Control of Integrin Expression by Extracellular Matrix

Abstract

Integrin-mediated interactions between cells and the extracellular matrix play a fundamental role in the development and function of a variety of tissues by triggering intracellular signals that regulate gene expression. In this study, mouse mammary epithelial cells plated on tissue culture plastic were shown to dramatically up-regulate the steady state levels of mRNA encoding the alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, alpha 7, alpha v, and beta 1 integrin subunits, in contrast to cells cultured on a basement membrane matrix or cells in vivo. This pattern of expression was also observed in a mouse mammary epithelial strain, CID-9 and in other mouse cell lines such as MMTE cells and K1735-M2 melanoma cells. The control of integrin expression was mediated at different levels in different cell types. In K1735-M2 cells, transcription of the beta 1 integrin gene was influenced by the substratum, although the levels of integrin protein remained similar. In mammary epithelial cells, the rates of beta 1 integrin gene transcription were similar, but mRNA and protein levels were higher in cells cultured on plastic than those on basement membrane. For both cell types, the rate of integrin protein turnover was nearly identical in cells cultured on either substratum. Our results demonstrate that extracellular matrix controls the expression of beta 1 integrin subunits and that this regulation is exerted at both transcriptional and post-transcriptional levels.