Ruth Lupu

Mayo Clinic - Rochester · Department of Experimental Medicine and Pathology

The initial excitement generated more than two decades ago by the discovery of drugs targeting fatty acid synthase (FASN)‐catalyzed de novo lipogenesis for cancer therapy was short‐lived. However, the advent of the first clinical‐grade FASN inhibitor (TVB‐2640; denifanstat), which is currently being studied in various phase II trials, and the excit...

Epithelial-to-mesenchymal transition (EMT) is key to tumor aggressiveness, therapy resistance, and immune escape in breast cancer. Because metabolic traits might be involved along the EMT continuum, we investigated whether human breast epithelial cells engineered to stably acquire a mesenchymal phenotype in non-tumorigenic and H-RasV12-driven tumor...

The HER3/4 ligand heregulin-β2 (HRG) is a secreted growth factor that transactivates the ligand-less receptor HER2 to promote aggressive phenotypes in breast cancer. HRG can also localize to the nucleus of breast cancer cells, but both the nuclear translocation mechanism and the physiological role of nuclear HRG remain elusive. Here we show that nu...

Introduction: Brain metastasis (BrM) is a key contributor to morbidity and mortality in breast cancer patients, especially among high-risk epidermal growth factor receptor 2-positive (HER2+) and triple-negative/basal-like molecular subtypes. Optimal management of BrM is focused on characterizing a "BrM dependency map" to prioritize targetable ther...

Triple-negative/basal-like breast cancer (BC) is characterized by aggressive biological features, which allow relapse and metastatic spread to occur more frequently than in hormone receptor-positive (luminal) subtypes. The molecular complexity of triple-negative/basal-like BC poses major challenges for the implementation of targeted therapies, and...

CCN1/CYR61 promotes angiogenesis, tumor growth and chemoresistance by binding to its integrin receptor αvβ3 in endothelial and breast cancer (BC) cells. CCN1 controls also tissue regeneration by engaging its integrin receptor α6β1 to induce fibroblast senescence. Here, we explored if the ability of CCN1 to drive an endocrine resistance phenotype in...

Inhibitors of the lipogenic enzyme fatty acid synthase (FASN) have attracted much attention in the last decade as potential targeted cancer therapies. However, little is known about the molecular determinants of cancer cell sensitivity to FASN inhibitors (FASNis), which is a major roadblock to their therapeutic application. Here, we find that pharm...

Simple Summary Overactivation of the human epidermal growth factor receptor 2 (HER2) is one of the main drivers of tamoxifen resistance in estrogen receptor (ER)-positive breast cancer patients. Combined targeting of HER2 and ER, however, has yielded disappointing results in the clinical setting. Therefore, other potential mechanisms for tamoxifen...

Progesterone receptor (PR) isoforms can drive unique phenotypes in luminal breast cancer (BC). Here, we hypothesized that PR-B and PR-A isoforms differentially modify the cross-talk between prolactin and fatty acid synthase (FASN) in BC. We profiled the responsiveness of the FASN gene promoter to prolactin in T47Dco BC cells constitutively expressi...

Sustained HER2/HER3 signaling due to the overproduction of the HER3 ligand heregulin (HRG) is proposed as a key contributor to endocrine resistance in estrogen receptor-positive (ER+) breast cancer. The molecular mechanisms linking HER2 transactivation by HRG-bound HER3 to the acquisition of a hormone-independent phenotype in ER+ breast cancer is,...

HER2 transactivation by the HER3 ligand heregulin (HRG) promotes an endocrine-resistant phenotype in the estrogen receptor-positive (ER+) luminal-B subtype of breast cancer. The underlying biological mechanisms that link them are, however, incompletely understood. Here, we evaluated the putative role of the lipogenic enzyme fatty acid synthase (FAS...

One of the greatest challenges in the cancer immunotherapy field is the need to biologically rationalize and broaden the clinical utility of immune checkpoint inhibitors (ICIs). The balance between metabolism and immune response has critical implications for overcoming the major weaknesses of ICIs, including their lack of universality and durabilit...

Fatty acid synthase (FASN) is a novel therapeutic target for cancer as it has increased expression in many different types of cancers. There has been significant understanding that cancer cells can hijack and modify tightly regulated metabolic pathway for its own survival. FASN is the enzyme that synthesizes palmitate from malonyl-CoA for energy st...

Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States and continues to be hindered with limited treatment options. One of the current therapeutic regimens for pancreatic cancer often include the nucleoside analog gemcitabine (Gem), while it has been used for many years, the overall survival rate lingers around...

Fatty Acid Synthase (FASN), the key multienzyme in de novo lipogenesis, is upregulated and activated in numerous carcinomas, including breast cancer. Fatty acids play a fundamental role in cellular structure, energy production and storage and are intermediates in the biosynthesis of hormones and other biologic molecules. Therefore, FASN is a novel...

Evidence is provided that the fibroproliferative actions of TGF-β are dependent on a metabolic adaptation that sustains pathologic growth. Specifically, profibrotic TGF-β signaling is shown to require fatty acid synthase (FASN), an essential anabolic enzyme responsible for the de novo synthesis of fatty acids. With the use of pharmacologic and gene...

Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capa...

Introduction: Ten years ago, we put forward the metabolo-oncogenic nature of fatty acid synthase (FASN) in breast cancer. Since the conception of this hypothesis, which provided a model to explain how FASN is intertwined with various signaling networks to cell-autonomously regulate breast cancer initiation and progression, FASN has received consid...

Purpose: Cilengitide is a potent and selective inhibitor of the integrins αvβ3 and αvβ5. The primary objective of this phase I clinical trial was to establish the maximum tolerated dose and determine safety/tolerability of cilengitide in combination with paclitaxel in patients with advanced solid tumors. Secondary objectives included the evaluatio...

Denosumab, a monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), might be a novel preventative therapy for BRCA1-mutation carriers at high risk of developing breast cancer. Beyond its well-recognized bone-targeted activity impeding osteoclastogenesis, denosumab has been proposed to interfere with the cross-talk betwee...

Fatty acid synthase (FASN), the key enzyme for endogenous synthesis of fatty acids, is overexpressed and hyperactivated in a biologically aggressive subset of sex steroid-related tumors, including breast carcinomas. Using pharmacological and genetic approaches, we assessed the molecular relationship between FASN signaling and estrogen receptor alph...

Fatty acid synthase (FASN) is a key lipogenic enzyme for de novo fatty acid biosynthesis and a druggable metabolic oncoprotein that is activated in most human cancers. We evaluated whether the HER2-driven lipogenic phenotype might represent a biomarker for sensitivity to pharmacological FASN blockade. A majority of clinically HER2-positive tumors w...

The angiogenic inducer CCN1 (Cysteine-rich 61, CYR61) is differentially activated in metastatic breast carcinomas. However, little is known about the precise mechanisms that underlie the pro-metastatic actions of CCN1. Here, we investigated the impact of CCN1 expression on fatty acid synthase (FASN), a metabolic oncogene thought to provide cancer c...

We hypothesized that women inheriting one germline mutation of the BRCA1 gene ("one-hit") undergo cell-type-specific metabolic reprogramming that supports the high biosynthetic requirements of breast epithelial cells to progress to a fully malignant phenotype. Targeted metabolomic analysis was performed in isogenic pairs of nontumorigenic human bre...

Alterations in cellular metabolism are known to play critical roles in a variety of normal as well as pathological processes, including (but not limited to) cancer, hepatic steatosis, and cell differentiation. While TGFβ is routinely considered a pleotropic cytokine due to its ability to impact numerous diseases and biological phenotypes, the role...

Polyphenols are a structural class of natural and synthetic organic chemicals which contain phenol units. Numerous epidemiological, preclinical and clinical studies have strongly supported their benefical effects for human health. Polyphenols group include molecules of utterly different complexity grades, ranging from simple moleculesto highly poly...

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA About 25% of breast carcinomas are characterized by over-expression and/or amplification of the HER2 receptor, one of four members of the HER family of receptor tyrosine kinases. The strong correlation between HER2 levels/activity with more aggressive breast cancer di...

The growth factor heregulin (HRG) promotes breast cancer (BC) tumorigenesis and metastasis and differentially modulates BC cell responses to DNA-damaging agents via its dual extracellular and nuclear localization. Given the central role of telomere dysfunction to drive carcinogenesis and to alter the chemotherapeutic profile of transformed cells, w...

Telomere length, shape and function depend on a complex of six core telomere-associated proteins referred to as the telosome or shelterin complex. We here demonstrate that the isoform β2 of the heregulin family of growth factors (HRGβ2) is a novel interactor of the telosome/shelterin complex in human telomeres. Analysis of protein-protein interacti...

Background: Several treatment strategies target the human epidermal growth factor receptor 2 (HER2) in breast carcinomas, including monoclonal antibodies directed against HER2's extracellular domain (ECD) and small molecule inhibitors of its tyrosine kinase activity. Yet, novel therapies are needed that prevent HER2 dimerization with other HER fam...

The HER2 receptor is over-expressed in about 25% of breast carcinomas and correlates with more aggressive breast cancer disease, poor prognosis as well as resistance to chemo- and endocrine therapies. The strong correlation between HER2 levels/activity and the malignancy of the disease made it a preferred target for anti-cancer therapy. For example...

Heregulin (HRG)s are high-affinity combinatorial ligands for the HER family of tyrosine kinase receptors. HRG induces heterodimerization and cross-talk between members of the HER tyrosine kinase receptor family. HRG interaction with HER3 induces heterodimerization between HER3 and other HER receptors, including epidermal growth factor receptor (EGF...

Increased de novo lipogenesis due to enhanced expression of several lipogenic enzymes has been found in many types of human cancers. Fatty acid synthase (FASN), the key enzyme in the de novo lipogenesis pathway, is one of the most commonly over-expressed lipogenic enzymes. Studies in the past decade have recognized FASN overexpression as a molecula...

Overcoming drug resistance, emerging either on recurring cancer or metastasis, is a major challenge of cancer treatments. The combination of anti-angiogenic agents with chemotherapeutic ones offers a promising therapeutic approach. Such combination can be achieved exploiting the multivalency of polymer therapeutics. We have recently showed that pol...

Heregulin (HRG), a combinatorial ligand for the epidermal growth factor receptor family, is expressed in about 30% of breast cancer tumors. HRG induces tumorigenicity and metastasis of breast cancer cells and promotes hormone-independent growth [1]. Although HRG has been studied mostly in the context of the HRG receptor family, accumulating evidenc...

Energy metabolism plasticity enables stemness programs during the reprogramming of somatic cells to an induced pluripotent stem cell (iPSC) state. This relationship may introduce a new era in the understanding of Warburg's theory on the metabolic origin of cancer at the level of cancer stem cells (CSCs). Here, we used Yamanaka's stem cell technolog...

Fatty acid synthase (FASN), the key enzyme in de novo lipogenesis, is significantly upregulated and activated in many carcinomas, including breast cancer. Pharmacological inhibition of FASN induces apoptosis of FASN expressing cancer cells. However, the mechanism is still unclear. Inhibition of FASN in breast cancer cells induces a dose dependent i...

Fatty acid synthase (FASN) is a lipogenic enzyme responsible for the novo synthesis of fatty acids (FAs) from acetyl-CoA and malonyl-CoA in a NADPH dependent manner in cells. FAs are essential constituents of all biological membranes lipids and are important substrates for energy metabolism. While normal cells (except liver and adiposities) express...

A crucial step in cancer progression is the development of a high-density vascular network, the angiogenic switch. During carcinogenesis breast angiogenesis occurs at hyperplasia before atypia, reaching maximum vascularization between ductal carcinoma in situ and invasive carcinoma. Altered energy metabolism is an early hallmark of several human ma...

High levels of plasminogen activator inhibitor-1 (PAI-1), which is produced by stromal, endothelial, and cancer cells and has multiple complex effects on cancers, correlate with poor cancer prognosis. To more definitively study the role of endogenously produced PAI-1 in human pancreatic adenocarcinoma (PAC) PANC-1 cell line biology, we used anti-PA...

Pancreatic cancer is the fourth leading cause of cancer deaths in the United States and continues to be a disease with few options for treatment. Current therapeutic regimens for pancreatic cancer often include the nucleoside analog gemcitabine (GEM), but while it has been in use for many years, the overall five year survival rate continues to be a...

Background: Cyr61, also known as CCN1, is a survival and pro-angiogenic factor overexpressed in invasive breast tumors that promotes tumorigenicity. We investigated whether Cyr61 plays important roles in breast cancer and evaluated its potential role as a chemotherapeutical target. Methods: We analyzed Cyr61 expression in a tissue microarray from b...

Overcoming drug resistance, emerging either on recurring cancer or metastasis, is a major target of cancer treatments. The combination of anti-angiogenic therapy with cytotoxic therapy offers a promising therapeutic approach. Paclitaxel (PTX) is a widely-used potent cytotoxic drug, which also exhibits anti-angiogenic activity at low doses. The use...

miRNA plays an important role in human disease and cancer. We seek to investigate the expression status, clinical relevance, and functional role of miRNA in non-small cell lung cancer. We conducted miRNA expression profiling in matched lung adenocarcinoma and uninvolved lung using 56 pairs of fresh-frozen (FF) and 47 pairs of formalin-fixed, paraff...

Induced pluripotent stem (iPS) cells share some basic properties, such as self-renewal and pluripotency, with cancer cells, and they also appear to share several metabolic alterations that are commonly observed in human tumors. The cancer cells' glycolytic phenotype, first reported by Otto Warburg, is necessary for the optimal routing of somatic ce...

CCN1, also known as CYR61, is a survival and proangiogenic factor overexpressed in about 30% of invasive breast carcinomas, and particularly in triple-negative breast carcinomas (TNBC). CCN1 expression in breast cancer promotes tumorigenicity, metastasis, antihormone, and chemoresistance. TNBCs often develop bone metastasis, thus the vast majority...

Heregulin internalization to the nucleus is mediated via binding to Nucleolin Lin Yang, and Ruth Lupu. Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation, Rochester, Minnesota 55902 Heregulin (HRG) is known as a soluble secreted growth factor of EGF-like family, which binds and activates HER3 and HER4 and transactivates HER2 an...

In pancreatic cancer both chemotherapy and radiotherapy have shown deficient results in treating the disease, indicating a fundamental need for more efficient therapies. Most pancreatic cancer patients present with an advanced form of the disease that is incurable by surgery, and will receive palliative treatment in the form of surgery, chemotherap...

Estrogen receptors (ERs) play key roles in breast cancer development and influence treatment outcome in breast cancer patients. More than 60% of human breast cancer tumors express ER and many of those are Estrogen (E2) dependent. ER positive tumors are considered to have a good prognosis; however some tumors escape to E2 requirements. Thus, the ide...

The growth factor Heregulin (HRG) is expressed in about 30% of breast cancer tumors, and induces tumorigenicity and metastasis of breast cancer cells. We have demonstrated previously that HRG overexpression renders breast cancer cells resistance to the microtubule-interfering agent Taxol, a drug of choice for the treatment of metastatic breast canc...

CYR61 render human breast cancer cells highly resistance to the microtubule-interfering agent Taxol, a drug of choice for the treatment of metastatic breast cancer. The angiogenic factor CYR61 and its receptor avβ3 are markedly up-regulated in very aggressive breast carcinomas. Integrin signaling has been shown to modulate cancer cell responses to...

Numerous solid tumors confirm increased expression of FASN. FASN expression is upregulated in early steps of breast cancer, such as DCIS, and is associated with poor clinical outcome in more advanced disease. The objective of this study is to evaluate FASN inhibition as a prevention of breast cancer progression and as an effective treatment of meta...

We have analyzed the gene modulation induced by zoledronic acid (ZOL) in androgen-resistant prostate cancer PC3 cells with cDNA microarray platform to identify new molecular targets of ZOL in prostate cancer. The gene coding for cysteine-rich, angiogenic inducer, 61 (CYR61) resulted highly downregulated with a fold change of 5.58. Therefore, we hav...

Fatty acid synthase (FASN) represents a metabolic oncogene. It produces phospholipids for membrane microdomains that accommodate receptor tyrosine kinases including Epidermal Growth Factor-Receptor (EGFR, ErbB1) and ErbB2 (HER2/neu). FASN and ErbBs are overexpressed in ovarian cancer. We examined the effect of FASN and ErbB inhibition on A2780 and...

We investigated the expression of transforming growth factors β1 and α (TGF-β1, TGF-α) in hormone-responsive (MPA-R) and unresponsive (MPA-U) tumor lines obtained from medroxyprogesterone acetate (MPA)-induced mammary adenocarcinomas in BALBIc mice. The tumors were transplanted into MPA-treated and untreated mice. TGF-β1 gene expression was observe...

#3074 Background: Cyr61, currently known as CCN1, is a pro-angiogenic factor highly expressed in triple negative breast carcinomas. CCN1 binds, among others, to αvβ3 integrin receptor, which is concomitantly expressed with CCN1 in triple negative carcinomas. It has clinically established that a greater part of the tumor initially diagnose as triple...

#2016 Background: Heregulins (HRGs) are known as soluble secreted growth factors that are involved via binding and activating HER3 and HER4 cell surface receptors in cell proliferation, metastasis, survival, and differentiation in normal and malignant tissues. We have previously shown that up-regulation of HRG is sufficient for development of mamma...

PANC-1 cells express proteinase-activated receptors (PARs)-1, -2, and respond to their activation by transient elevation of cytosolic [Ca(2+)] and accelerated aggregation (Wei et al., 2006, J Cell Physiol 206:322-328). We studied the effect of plasminogen (PGN), an inactive precursor of the PAR-1-activating protease, plasmin (PN) on aggregation of...

Fatty acid synthase (FASN) is a novel druggable target for metabolically treating and preventing human malignancies. We envisioned that if loss of sensitivity to C75 (a slow-binding FASN inhibitor) occurs in parallel with loss of FASN expression and/or activity, a mathematical assessment of the nature of the interaction between investigational FASN...

More than 50 years ago, we learned that breast cancer cells (and those of many other types of tumour) endogenously synthesize 95% of fatty acids (FAs) de novo, despite having adequate nutritional lipid supply. Today, we know that breast cancer cells benefit from this phenomenon in terms of enhanced cell proliferation, survival, chemoresistance and...

We are accumulating evidence to suggest that 17th century Renaissance foodways-largely based on the old “Mediterranean dietary traditions”-may provide new nutraceutical management strategies against HER2-positive breast cancer disease in the 21st century. Epidemiological and experimental studies begin to support the notion that “The Sacred Law of S...

alpha(v)beta(3) integrin has a dual role in apoptosis. Whereas ligated alpha(v)beta(3) activates cell survival pathways and suppresses pro-apoptotic signals, unligated alpha(v)beta(3) or integrins bound to soluble ligands promote apoptosis. In this study, we assessed the role of alpha(v)beta(3) in chemosensitivity of breast cancer cells expressing...

There is a renewed interest in the ultimate role of fatty acid synthase (FASN)--a key lipogenic enzyme catalysing the terminal steps in the de novo biogenesis of fatty acids--in cancer pathogenesis. Tumour-associated FASN, by conferring growth and survival advantages rather than functioning as an anabolic energy-storage pathway, appears to necessar...

Targeting HER2 is not as straightforward as it was originally predicted since many breast tumors express multiple HER receptors and co-express one or more HER ligands. This cross-talk network negatively impacts the response to the currently used HER2-targeted agents, highlighting the urgent need for a novel anti-HER2 molecule(s) presenting a combin...

Although neither kinase-dead human epidermal growth factor receptor (HER)3 nor orphan HER2 can be activated by HER-related ligands on their own, the formation of HER2/HER3 heterodimers creates the most mitogenic and transforming receptor complex within the HER (erbB) family of transmembrane receptor tyrosine kinases. The incorporation of markers su...

The expression and activity of Fatty Acid Synthase (FASN; the sole enzyme capable of the reductive de novo synthesis of long-chain fatty acids from acetyl-CoA, malonyl-CoA, and nicotinamide adenine dinucleotide phosphate -NADPH-) is extremely low in nearly all nonmalignant adult tissues, whereas it is significantly up-regulated or activated in many...

The final proof about the specific mechanisms by which the different components of olive oil, the principal source of fat in a typical "Mediterranean diet", exert their potential protective effects on the promotion and progression of several human cancers requires further investigations. A recent discovery that dietary fatty acids can interact with...

Fatty acid synthase (FAS), the key metabolic multi-enzyme that is responsible for the terminal catalytic step in the de novo fatty acid biosynthesis, plays an active role in the development, maintenance, and enhancement of the malignant phenotype in a subset of breast carcinomas. We recently described that a molecular bi-directional cross-talk betw...

Data derived from epidemiological and experimental studies suggest that alphalinolenic acid (ALA; 18:3n-3), the main omega-3 polyunsaturated fatty acid (PUFA) present in the Western diet, may have protective effects in breast cancer risk and metastatic progression. A recent pilot clinical trial assessing the effects of ALA-rich dietary flaxseed on...

Olive oil is an integral ingredient of the "Mediterranean diet" and accumulating evidence suggests that it may have a potential role in lowering risk of several cancers. We recently hypothesized that the anti-cancer actions of olive oil may relate to its monounsaturated fatty acid (MUFA) oleic acid (OA; 18:1n-9) content to specifically regulate onc...

There is an urgent need to identify and develop a new generation of therapeutic agents and systemic therapies targeting the estradiol (E2)/estrogen receptor (ER) signaling in breast cancer. In this regard, new information on the mechanisms of E2/ER function and/or cross talk with other prosurvival cascades should provide the basis for the developme...

In addition to their role in cell migration and adhesion, integrins elicit a series of transduction events that regulate cell-cycle progression and apoptosis in a process known as "outside-in" signaling. A second mode of integrin regulation known as "inside-out" signaling, in which the activation of major cell transduction cascades can influence th...

The decision for treating breast cancer patients with trastuzumab is based on HER-2 amplification and/or overexpression. Using MCF-7 cells (Her-2 +/-) engineered to overexpress heregulin (MCF-7/HRG), a ligand for the Her-2/3/4 network, we investigated whether HRG-induced transactivation of Her-2 affected breast cancer cell sensitivity to chemothera...

This review documents our rapidly changing perspectives on the function of fatty acid synthase-catalyzed endogenous fatty acid biogenesis in cancer biology. Up-regulation of fatty acid synthase gene expression and fatty acid synthase biosynthetic activity are molecular events accompanying the pathogenesis and natural history of cancer disease. Firs...

Menendez JA, Vellon L, Lupu R. The antiobesity drug Orlistat induces cytotoxic effects, suppresses Her-2/neu (erbB-2) oncogene overexpression, and synergistically interacts with trastuzumab (Herceptin™) in chemoresistant ovarian cancer cells. Int J Gynecol Cancer 2006;16:219–221.

The ω-6 polyunsaturated fatty acid γ-linolenic acid (GLA; 18:3n-6), which is found in several plant oils and is used as an herbal medicine, has antitumor activity in vitro. We examined the effect of GLA on the expression of the Her-2/neu (erbB-2) oncogene, which is involved in development of numerous types of human cancer. Flow cytometric and immun...

Orlistat (Xenicaltrade mark), a US Food and Drug Administration (FDA)-approved drug for bodyweight loss, has recently been demonstrated to exhibit antitumor properties towards prostate cancer cells by virtue of its ability to block the lipogenic activity of fatty acid synthase (FAS). FAS (oncogenic antigen-519) is up-regulated in about 50% of breas...

Fatty acid synthase (FAS)-catalyzed de novo fatty acid biosynthesis, an anabolic energy-storage pathway largely considered of minor importance in humans, actively contributes to the cancer phenotype by virtue of its ability to specifically regulate the expression and activity of Her-2/neu (erbB-2) oncogene. First, a positive correlation between hig...

Omega-3 polyunsaturated fatty acid (PUFA), docosahexaenoic acid (DHA; 22:6n-3) and other omega-3 and omega-6 PUFAs have raised interest as novel anticancer agents by exerting selective cytotoxic effects on human cancer cells without affecting normal tissues. Here, we examined the in vitro relationship between exogenous supplementation with DHA and...

Overexpression of the lipogenic enzyme fatty acid synthase (FAS) is a common molecular feature in subsets of sex-steroid-related tumors including breast carcinomas that is associated with poor prognosis. In this study, we explored whether breast-cancer associated FAS (oncogenic antigen-519) is regulated by the progestin component in oral contracept...

alpha(v)beta(3) integrin-overexpression in tumor associated vasculature is a marker of poor prognosis in breast cancer. A positive correlation between alpha(v)beta(3) integrin and overexpression of Heregulin (HRG), a growth factor associated with breast cancer aggressiveness was recently demonstrated. Here, we addressed the role of alpha(v)beta(3)...

The relationship between breast cancer-associated fatty acid synthase (FAS; oncogenic antigen-519) and chemotherapy-induced cell damage has not been studied. We examined the ability of C75, a synthetic slow-binding inhibitor of FAS activity, to modulate the cytotoxic activity of the microtubule-interfering agent Taxol (paclitaxel) in SK-Br3, MDA-MB...

Elevated levels of p21WAF1/CIP1, an important mediator of DNA repair, have been observed in various aggressive tumors as well as linked to chemoresistance. We examined whether heregulin (HRG), a member of the EGF-like growth factor family closely related to breast cancer tumorigenesis and metastasis, modulates p21WAF1/CIP1 expression and cellular l...

Her-2/neu (erbB-2) oncogene overexpression is associated with increased tumor progression and metastasis. Fatty acid synthase (FAS), the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids, has been shown to be one of the genes regulated by Her-2/neu at the level of transcription, translation, and biosynthetic activity. Int...