Up-regulation of alpha(v)beta(3) integrin expression is a novel molecular response to chemotherapy-induced cell damage in a heregulin-dependent manner.

Up-regulation of alpha(v)beta(3) integrin expression is a novel molecular response to chemotherapy-induced cell damage in a heregulin-dependent manner. Research Abstract Details 

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Up-regulation of alpha(v)beta(3) integrin expression is a novel molecular response to chemotherapy-induced cell damage in a heregulin-dependent manner. Abstract Text:

Luciano Vellon,Javier A Menendez,Hong Liu,Ruth Lupu,Luciano Vellon,Javier A Menendez,Hong Liu,Ruth Lupu,Luciano Vellon,Javier A Menendez,Hong Liu,Ruth Lupu,

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 different levels of heregulin (HRG). Expression levels of the RGD-binding integrins alpha(v)beta(3) were measured in MDA-MB-231 human breast cancer cells and its low HRG-expressing derivative (MDA-MB-231/AS31) treated with the microtubule-interfering agents (MIAs) paclitaxel and vincristine. Following treatment, only alpha(v)beta(3) levels were significantly increased in MDA-MB-231 cells. Interestingly, alpha(v)beta(3) expression was more significantly up-regulated in the MDA-MB-231/AS31 cells than in the parental cells. This MIA-induced increase of alpha(v)beta(3) expression was correlated with a decrease in cell viability and an increase in apoptosis in MDA-MB-231/AS31 cells, indicating that overexpression of alpha(v)beta(3) is linked to chemotherapy-induced cell death in low HRG-expressing breast cancer models. Moreover, a paclitaxel-induced increase of alpha(v)beta(3) was also observed in MCF-7 cells but not in an doxorubicin-resistant derivative that shows cross-resistance to paclitaxel, further providing evidence that the extent of alpha(v)beta(3) up-regulation is related to cell damage. These results indicate that alpha(v)beta(3) integrin is dramatically up-regulated in low HRG-expressing breast cancer models that are highly responsive to MIAs, thus providing a novel molecular marker of chemosensitivity influenced by HRG levels in breast cancer cells.

Up-regulation of alpha(v)beta(3) integrin expression is a novel molecular response to chemotherapy-induced cell damage in a heregulin-dependent manner. Publishing Authors By Initials

L Vellon,JA Menendez,H Liu,R Lupu,L Vellon,JA Menendez,H Liu,R Lupu,L Vellon,JA Menendez,H Liu,R Lupu,

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Up-regulation of alpha(v)beta(3) integrin expression is a novel molecular response to chemotherapy-induced cell damage in a heregulin-dependent manner. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Differentiation; research in biological diversity

VOLUME: 75

Page Numbers: 819-30

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ISSN: 0301-4681

DAY: 16

MONTH: Nov

YEAR: 2007

Up-regulation of alpha(v)beta(3) integrin expression is a novel molecular response to chemotherapy-induced cell damage in a heregulin-dependent manner. Information

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LANGUAGE: eng

NlmUniqueID: 401650

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Grant and Affiliation Information for Up-regulation of alpha(v)beta(3) integrin expression is a novel molecular response to chemotherapy-induced cell damage in a heregulin-dependent manner.

AFFILIATION: Department of Medicine, Breast Cancer Translational Research Laboratory, Evanston Northwestern Healthcare Research Institute, 1001 University Place, Evanston, IL, USA, and Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Country: England

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MEDLINETA: Differentiation

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