Differentiation of mammary epithelial cells by a laminin-rich basement membrane alters the splicing pattern of different cancer and inflammation related genes

QUAGLINO, ANA; RISSO, GUILLERMO; SREBROW ANABELLA

Iguazu, Misiones

Congreso; Gene Expression and RNA Processing; 2011

ICGEB, ANPCyT y CONICET

<!-- /* Font Definitions */ @font-face {font-family:Times; panose-1:2 0 5 0 0 0 0 0 0 0; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:3 0 0 0 1 0;} @font-face {font-family:"Cambria Math"; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:-536870145 1107305727 0 0 415 0;} @font-face {font-family:Cambria; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:-536870145 1073743103 0 0 415 0;} @font-face {font-family:"MS Minngs"; panose-1:0 0 0 0 0 0 0 0 0 0; mso-font-alt:"MS Mincho"; mso-font-charset:128; mso-generic-font-family:roman; mso-font-format:other; mso-font-pitch:fixed; mso-font-signature:1 134676480 16 0 131072 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:Cambria; mso-fareast-font-family:"MS Minngs"; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:EN-US;} .MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-size:11.0pt; mso-ansi-font-size:11.0pt; mso-bidi-font-size:11.0pt; font-family:Cambria; mso-ascii-font-family:Cambria; mso-fareast-font-family:"MS Minngs"; mso-hansi-font-family:Cambria; mso-ansi-language:ES-AR; mso-fareast-language:ES-AR;} @page WordSection1 {size:612.0pt 792.0pt; margin:72.0pt 90.0pt 72.0pt 90.0pt; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.WordSection1 {page:WordSection1;} --> Extracellular Matrix (ECM) modulates tissue homeostasis of the mammary gland in vivo, and growth, differentiation, and apoptosis of mammary epithelial (ME) cells in culture. Considering that the regulation of alternative splicing (AS) by extracellular signals represents a key event in the control of gene expression, our group has used a well described cell culture model of mouse mammary epithelial differentiation to demostrate that a laminin rich basement membrane (lr-BM) stimulates exclusion of two alternative regions (EDA and IIICS) from fibronectin mRNA (1). To broaden our knowledge about the regulation of AS by the ECM, we used an automated high-throughput RT-PCR platform (2 and screen 140 AS events selected by their possible connection with cell fate, mammary gland and cancer biology, in differentiated vs. undifferentiated ME cells (2). Interestingly, we found that the lr-BM triggered significant changes in the splicing pattern of several pre-mRNAs involved in breast cancer and inflammatory processes. Furthermore, many of the AS changes observed between differentiated and undifferentiated ME cells were similar to that found between lactating and involuting mammary glands in vivo. Noteworthy, during involution the expression profile of many genes is similar to that found in breast tumors and also the activation of inflammatory processes has been reported. Based on these results, we propose to dissect the molecular mechanisms by which these AS events are regulated by lr-BM in ME cells and explore the cellular and tisular consequences of altering the ratio between the different splicing isoforms.