p18Ink4c and Pten constrain a positive regulatory loop between cell growth and cell cycle control Journal Article
| Authors: | Bai, F.; Pei, X. H.; Pandolfi, P. P.; Xiong, Y. |
| Article Title: | p18Ink4c and Pten constrain a positive regulatory loop between cell growth and cell cycle control |
| Abstract: | Inactivation of the Rb-mediated G1 control pathway is a common event found in many types of human tumors. To test how the Rb pathway interacts with other pathways in tumor suppression, we characterized mice with mutations in both the cyclin-dependent kinase (CDK) inhibitor p18Ink4c and the lipid phosphatase Pten, which regulates cell growth. The double mutant mice develop a wider spectrum of tumors, including prostate cancer in the anterior and dorsolateral lobes, with nearly complete penetrance and at an accelerated rate. The remaining wild-type allele of Pten was lost at a high frequency in Pten+/- cells but not in p18+/- Pten+/- or p18-/- Pten+/- prostate tumor cells, nor in other Pten+/- tumor cells, suggesting a tissue- and genetic background-dependent haploinsufficiency of Pten in tumor suppression. p18 deletion, CDK4 overexpression, or oncoviral inactivation of Rb family proteins caused activation of Akt/PKB that was recessive to the reduction of PTEN activity. We suggest that p18 and Pten cooperate in tumor suppression by constraining a positive regulatory loop between cell growth and cell cycle control pathways. Copyright © 2006, American Society for Microbiology. All Rights Reserved. |
| Keywords: | signal transduction; protein kinase b; controlled study; protein expression; unclassified drug; nonhuman; protein function; cell proliferation; animal cell; mouse; mouse mutant; animals; mice; mice, knockout; allele; animal tissue; gene; cell cycle; cell growth; animal experiment; mice, mutant strains; mice, inbred c57bl; prostate cancer; prostatic neoplasms; cancer inhibition; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; proto-oncogene proteins c-akt; pten phosphohydrolase; growth regulation; thyroid neoplasms; cyclin dependent kinase inhibitor; cell cycle regulation; retinoblastoma protein; cell cycle g1 phase; adrenal gland neoplasms; cyclin dependent kinase inhibitor 2c; penetrance; pten gene; cyclin-dependent kinase inhibitor p18; pituitary neoplasms; protein p18 |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 26 |
| Issue: | 12 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2006-06-01 |
| Start Page: | 4564 |
| End Page: | 4576 |
| Language: | English |
| DOI: | 10.1128/mcb.00266-06 |
| PUBMED: | 16738322 |
| PROVIDER: | scopus |
| PMCID: | PMC1489117 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 25" - "Export Date: 4 June 2012" - "CODEN: MCEBD" - "Source: Scopus" |
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