We previously reported that ductal infiltrating carcinomas (d.i.c.) of the human breast display profound modifications of the stromal architecture, associated with anomalous collagen composition. Among the major alterations observed in the interstitial collagen, the relative increase of type V collagen content was detected. When type V collagen was used as an “in vitro” substrate for 8701-BC d.i.c. cells, it appeared able to restrain cell growth, inhibit cell motility and invasion “in vitro”, and modify the expression levels of genes coding for apoptosis factors, caspases and stress response proteins. In the present paper we demonstrate that type V collagen induces the down-regulation of protein kinase C η, an event that may be, at least in part, responsible of the previously-reported modifications of cell morphology and growth rate, and that appears to be involved in the already-observed changes of expression levels of genes encoding for anti- (Bcl-2) and pro-apoptotic factors (Bad, Dapk, Bcl-Xs) and enzymes (caspase 5 and 8). © 2011 Wiley Periodicals, Inc.