p16INK4a modulates p53 in primary human mammary epithelial cells - PubMed (original) (raw)
p16INK4a modulates p53 in primary human mammary epithelial cells
Jianmin Zhang et al. Cancer Res. 2006.
Free article
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.
Similar articles
- The role of Ink4a/Arf in ErbB2 mammary gland tumorigenesis.
D'Amico M, Wu K, Di Vizio D, Reutens AT, Stahl M, Fu M, Albanese C, Russell RG, Muller WJ, White M, Negassa A, Lee HW, DePinho RA, Pestell RG. D'Amico M, et al. Cancer Res. 2003 Jun 15;63(12):3395-402. Cancer Res. 2003. PMID: 12810676 - Co-transfection of p16(INK4a) and p53 genes into the K562 cell line inhibits cell proliferation.
Rui HB, Su JZ. Rui HB, et al. Haematologica. 2002 Feb;87(2):136-42. Haematologica. 2002. PMID: 11836163 - p16(INK4a) inactivation is not required to immortalize human mammary epithelial cells.
Herbert BS, Wright WE, Shay JW. Herbert BS, et al. Oncogene. 2002 Nov 7;21(51):7897-900. doi: 10.1038/sj.onc.1205902. Oncogene. 2002. PMID: 12420227 - The tumor suppressor protein p16INK4a.
Serrano M. Serrano M. Exp Cell Res. 1997 Nov 25;237(1):7-13. doi: 10.1006/excr.1997.3824. Exp Cell Res. 1997. PMID: 9417860 Review. - The INK4a/ARF network in tumour suppression.
Sherr CJ. Sherr CJ. Nat Rev Mol Cell Biol. 2001 Oct;2(10):731-7. doi: 10.1038/35096061. Nat Rev Mol Cell Biol. 2001. PMID: 11584300 Review.
Cited by
- Cell-type specific DNA methylation patterns define human breast cellular identity.
Novak P, Stampfer MR, Munoz-Rodriguez JL, Garbe JC, Ehrich M, Futscher BW, Jensen TJ. Novak P, et al. PLoS One. 2012;7(12):e52299. doi: 10.1371/journal.pone.0052299. Epub 2012 Dec 20. PLoS One. 2012. PMID: 23284978 Free PMC article. - Simultaneous expression of MMB-FOXM1 complex components enables efficient bypass of senescence.
Kumari R, Hummerich H, Shen X, Fischer M, Litovchick L, Mittnacht S, DeCaprio JA, Jat PS. Kumari R, et al. Sci Rep. 2021 Nov 2;11(1):21506. doi: 10.1038/s41598-021-01012-z. Sci Rep. 2021. PMID: 34728711 Free PMC article. - Dynamic regulation of CTCF stability and sub-nuclear localization in response to stress.
Lehman BJ, Lopez-Diaz FJ, Santisakultarm TP, Fang L, Shokhirev MN, Diffenderfer KE, Manor U, Emerson BM. Lehman BJ, et al. PLoS Genet. 2021 Jan 7;17(1):e1009277. doi: 10.1371/journal.pgen.1009277. eCollection 2021 Jan. PLoS Genet. 2021. PMID: 33411704 Free PMC article. - Molecular distinctions between stasis and telomere attrition senescence barriers shown by long-term culture of normal human mammary epithelial cells.
Garbe JC, Bhattacharya S, Merchant B, Bassett E, Swisshelm K, Feiler HS, Wyrobek AJ, Stampfer MR. Garbe JC, et al. Cancer Res. 2009 Oct 1;69(19):7557-68. doi: 10.1158/0008-5472.CAN-09-0270. Epub 2009 Sep 22. Cancer Res. 2009. PMID: 19773443 Free PMC article. - Immortalization of normal human mammary epithelial cells in two steps by direct targeting of senescence barriers does not require gross genomic alterations.
Garbe JC, Vrba L, Sputova K, Fuchs L, Novak P, Brothman AR, Jackson M, Chin K, LaBarge MA, Watts G, Futscher BW, Stampfer MR. Garbe JC, et al. Cell Cycle. 2014;13(21):3423-35. doi: 10.4161/15384101.2014.954456. Cell Cycle. 2014. PMID: 25485586 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous