Integrins are a large family of transmembrane receptors that, in addition to mediating cell adhesion, modulate cell proliferation. The β1C integrin is an alternatively spliced variant of the β1 subfamily that contains a unique 48–amino acid sequence in its cytoplasmic domain. We have shown previously that in vitro β1C inhibits cell proliferation and that in vivo β1C is expressed in nonproliferative, differentiated epithelium and is selectively downregulated in prostatic adenocarcinoma. Here we show, by immunohistochemistry and immunoblotting analysis, that β1C is coexpressed in human prostate epithelial cells with the cell-cycle inhibitor p27kip1, the loss of which correlates with poor prognosis in prostate cancer. In the 37 specimens analyzed, β1C and p27kip1 are concurrently expressed in 93% of benign and 84%–91% of tumor prostate cells. Forced expression of β1Cin vitro is accompanied by an increase in p27kip1 levels, by inhibition of cyclin A–dependent kinase activity, and by increased association of p27kip1 with cyclin A. β1C inhibitory effect on cell proliferation is completely prevented by p27kip1 antisense, but not mismatch oligonucleotides. β1C expression does not affect either cyclin A or E levels, or cyclin E–associated kinase activity, nor the mitogen-activated protein (MAP) kinase pathway. These findings show a unique mechanism of cell growth inhibition by integrins and point to β1C as an upstream regulator of p27kip1 expression and, therefore, a potential target for tumor suppression in prostate cancer.
Mara Fornaro, Giovanni Tallini, Duo-Qi Zheng, W. Michael Flanagan, Michela Manzotti, Lucia R. Languino
Usage data is cumulative from May 2023 through May 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 139 | 11 |
77 | 11 | |
Figure | 85 | 7 |
Table | 6 | 0 |
Citation downloads | 8 | 0 |
Totals | 315 | 29 |
Total Views | 344 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.