Raf-1-induced growth arrest in human mammary epithelial cells is p16-independent and is overcome in immortal cells during conversion.

摘要: Using an estrogen-inducible retroviral system, we demonstrate that oncogenic Raf-1 induces growth arrest and morphological changes in finite lifespan human mammary epithelial cells (HMEC). This does not rely on expression of the cyclin-dependent kinase inhibitor (CKI) p16INK4a, nor CKIs p21Cip1, p14ARF, p27Kip1 or p57Kip2. The Raf-induced is independent viral oncogene mediated inactivation p53 pRB, c-myc overexpression. Flow cytometric analysis demonstrates both G1 G2. mitigated eliminated some immortally transformed HMEC. Immortal HMEC have overcome replicative senescence undergone recently described conversion process maintain presence transduced Raf-1; they also gain EGF-independent a low frequency anchorage-independent growth. However, but immortalized by transduction with catalytic subunit telomerase, hTERT, remain severely arrested. These results indicate molecular mechanisms responsible for Raf-1-induced may vary among different cell types, HMEC, this mechanism altered during process, rather than as direct consequence overcoming expressing hTERT.