title: p16INK4a modulates p53 in primary human mammary epithelial cells.
abstract: p16(INK4a) (p16) and p53 are tumor suppressor genes that are inactivated during carcinogenesis in many tumors. Here we show that p16 gene activity inversely modulates p53 status and function in primary human mammary epithelial cells. Reduced levels of p16 protein stabilize p53 protein through inhibition of proteolytic degradation, and this increase in p53 protein levels enhances the cellular response to radiation, represses proliferation, and transcriptionally activates downstream targets. Stabilization of p53 is mediated through the retinoblastoma/E2F/p14(ARF)/murine double minute-2 pathway. However, we have observed that p16 does not modulate p53 in fibroblasts, indicating a possible cell type-specific regulation of this pathway.
authors.affiliation: Department of Pathology and UCSF Comprehensive Cancer Center, University of California San Francisco, California 94143, USA.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhang
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Pickering
authors.forename: Charles R
authors.initials: CR
authors.lastname: Holst
authors.forename: Mona L
authors.initials: ML
authors.lastname: Gauthier
authors.forename: Thea D
authors.initials: TD
authors.lastname: Tlsty
mesh_terms: D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000209:etiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D019942:Genes, p16; D006801:Humans; D016160:Retinoblastoma Protein / Q000502:physiology; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000502:physiology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53