Relevance of the 3’ untranslated region (3’UTR) in mammary gland b1-integrin expresión.

GATTELLI A.; NAIPAUER J.; LAMARRE J.; COSO O.; KORDON E.

Cioccio, Italia

Congreso; Gordon Research Conference in Mammary Gland.; 2008

Integrins belong to a super family of cell surface adhesion receptors that play a relevant role during normal development and tumor formation in the mammary gland. We examined gene products of b1 integrin in normal and neoplastic tissue by 3’RACE-PCR. By cloning and sequencing these reaction products, we found a new b1-integrin mRNA species, which arises from the use of an alternative polyadenylation site located 578 bp upstream from the previously reported one. Our analysis also revealed two AU-rich element (ARE) sequences implicated in the regulation of mRNA levels, localized between those sites and, therefore, absent in the shorter mRNA species. We determined that both mRNA forms are present in normal and neoplastic tissue, with a specific ratio corresponding to each physiological condition. We have sub-cloned the corresponding 3’UTR sequences for the two mRNAs into reporter vectors downstream of a CMV driven luciferase gene. Then, mRNA stability assays were performed. The results indicated that the longer form is less stable, suggesting that the ARE sequences may play a relevant role on the stability of this mRNA. Taken together, these data indicate that the presence of alternative 3’UTR regulating sequences may provide another regulatory instance to determine more precisely the b1-integrin abundance required in the different dynamic physiological situations occurring in the mammary gland.