Abstract C30: Laminin-5 expression in breast cancer culture cells after chemotherapic exposure
Authors: Zuccari Debora A P C , Castro Rodrigo , da Silva Leonel Camila , Jardim Bruna Victorasso , Gelaleti Gabriela Bottaro , Regiani Vitor Rafael , Moschetta Marina Gobbe 
Published: May 2012

Introduction: Laminin-5, a large heterotrimeric glycoprotein consisting of an alpha 3, beta 3, and gamma 2 chain, is a component of epithelial cell basement membranes that functions as a ligand of the alpha 3 beta 1 and alpha 6 beta 4 integrins to regulate cell adhesion, migration, and morphogenesis. Laminins also regulate cellular movement, growth and differentiation, induce inflammatory cells and integrate the extracellular matrix to epithelia. It is suspect to be a tumor suppressor gene in breast cancer resulting in inhibition of tumor metastasis. In contrast, recent studies describe that as a modify and metastatic gene. The importance of laminin-5 in the development of a variety of cancers makes it an attractive target for cancer therapeutics. This study was conducted to determine the laminin-5 expression after exposure to routine chemotherapy in breast carcinoma culture cells. The concept is that laminin-5 expression change after doxorubicin exposure. Studying chemotherapy-induced gene expression changes in vitro could provide insights into mechanisms of chemotherapy resistance.

Material and Methods: Doxorubicin exposure was performed on tumor tissue obtained from ten newly diagnosed carcinoma. The gene expression was determined before and after doxorubicin aggression. PCR amplifications were performed using a 7500 Fast Real-Time PCR System (Applied Biosystems). The gene expression stability over different samples was analyzed using the geNorm software.

Results: The cells were cultured for about 30 days. Then their origin was proof by immunohistochemical procedure using citoqueratin and vimentin. After that, the curve of growth was made after exposure to doxorubicin. There was distinct expression of laminin 5 in breast cancer culture cells. When the molecular study was concern there were statistical correlation between the gene expression and the drug resistance.

Discussion and Conclusion: Laminin-5 has abnormal expression and its integrin receptors are hallmark of certain tumor types and are believed to promote invasion of colon, breast and skin cancer cells. In invasive cancers, laminins usually become discontinuous or absent around tumor foci, which is attributed to either increased degradation or reduced synthesis. The importance of laminin-5 in the development of a variety of cancers makes it an attractive target for cancer therapeutics. However, laminin-5 based cancer therapies are not without their problems since treatments of necessity must target tumor laminin-5 but not laminin-5 in normal tissues since the latter is essential for maintaining tissue integrity. Future development of new reagents that inhibit the ability of laminin-5 to drive tumor growth and/or dissemination will be greatly facilitated once we better understand not only the precise regulation of laminin-5 proteolytic processing but also the different signaling cascades regulated by laminin-5 in normal versus tumor cells. Gene expression alterations of breast cancer were specific to doxorubicin treatment, and yielded mechanistic insights into resistance to the drug. Gene expression analysis provides more global perspectives on resistance pathways that could be exploited for therapeutic selection. Consideration of these factors should be incorporated in clinical practice after appropriate validation studies are performed to avoid confounding results, making them true prognostic and predictive factors.

Financing agency: FAPESP

Citation Information: Cancer Res 2009;69(23 Suppl):C30.