G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells - PubMed (original) (raw)

. 2004 Aug;287(2):C281-91.

doi: 10.1152/ajpcell.00422.2003. Epub 2004 Mar 17.

Affiliations

• PMID: 15028555
• DOI: 10.1152/ajpcell.00422.2003

Free article

G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells

Ning Gao et al. Am J Physiol Cell Physiol. 2004 Aug.

Free article

Abstract

Ovarian cancer is one of the most common cancers among women. Recent studies demonstrated that the gene encoding the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K) is frequently amplified in ovarian cancer cells. PI3K is involved in multiple cellular functions, including proliferation, differentiation, antiapoptosis, tumorigenesis, and angiogenesis. In this study, we demonstrate that the inhibition of PI3K activity by LY-294002 inhibited ovarian cancer cell proliferation and induced G(1) cell cycle arrest. This effect was accompanied by the decreased expression of G(1)-associated proteins, including cyclin D1, cyclin-dependent kinase (CDK) 4, CDC25A, and retinoblastoma phosphorylation at Ser(780), Ser(795), and Ser(807/811). Expression of CDK6 and beta-actin was not affected by LY-294002. Expression of the cyclin kinase inhibitor p16(INK4a) was induced by the PI3K inhibitor, whereas steady-state levels of p21(CIP1/WAF1) were decreased in the same experiment. The inhibition of PI3K activity also inhibited the phosphorylation of AKT and p70S6K1, but not extracellular regulated kinase 1/2. The G(1) cell cycle arrest induced by LY-294002 was restored by the expression of active forms of AKT and p70S6K1 in the cells. Our study shows that PI3K transmits a mitogenic signal through AKT and mammalian target of rapamycin (mTOR) to p70S6K1. The mTOR inhibitor rapamycin had similar inhibitory effects on G(1) cell cycle progression and on the expression of cyclin D1, CDK4, CDC25A, and retinoblastoma phosphorylation. These results indicate that PI3K mediates G(1) progression and cyclin expression through activation of an AKT/mTOR/p70S6K1 signaling pathway in the ovarian cancer cells.

PubMed Disclaimer

Similar articles

• Short-period hypoxia increases mouse embryonic stem cell proliferation through cooperation of arachidonic acid and PI3K/Akt signalling pathways.
  Lee SH, Lee MY, Han HJ. Lee SH, et al. Cell Prolif. 2008 Apr;41(2):230-47. doi: 10.1111/j.1365-2184.2008.00516.x. Cell Prolif. 2008. PMID: 18336469 Free PMC article.
• Role of PI3K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer.
  Gao N, Zhang Z, Jiang BH, Shi X. Gao N, et al. Biochem Biophys Res Commun. 2003 Oct 31;310(4):1124-32. doi: 10.1016/j.bbrc.2003.09.132. Biochem Biophys Res Commun. 2003. PMID: 14559232
• Longitudinal inhibition of PI3K/Akt/mTOR signaling by LY294002 and rapamycin induces growth arrest of adult T-cell leukemia cells.
  Ikezoe T, Nishioka C, Bandobashi K, Yang Y, Kuwayama Y, Adachi Y, Takeuchi T, Koeffler HP, Taguchi H. Ikezoe T, et al. Leuk Res. 2007 May;31(5):673-82. doi: 10.1016/j.leukres.2006.08.001. Epub 2006 Sep 27. Leuk Res. 2007. PMID: 17007924
• The molecular target of rapamycin (mTOR) as a therapeutic target against cancer.
  Mita MM, Mita A, Rowinsky EK. Mita MM, et al. Cancer Biol Ther. 2003 Jul-Aug;2(4 Suppl 1):S169-77. Cancer Biol Ther. 2003. PMID: 14508096 Review.
• Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.
  Liang J, Slingerland JM. Liang J, et al. Cell Cycle. 2003 Jul-Aug;2(4):339-45. Cell Cycle. 2003. PMID: 12851486 Review.

Cited by

• Expression of phosphorylated mTOR and its regulatory protein is related to biological behaviors of ameloblastoma.
  Li N, Zhong M, Song M. Li N, et al. Int J Clin Exp Pathol. 2012;5(7):660-7. Epub 2012 Sep 5. Int J Clin Exp Pathol. 2012. PMID: 22977662 Free PMC article.
• Combining mTOR inhibition with radiation improves antitumor activity in bladder cancer cells in vitro and in vivo: a novel strategy for treatment.
  Nassim R, Mansure JJ, Chevalier S, Cury F, Kassouf W. Nassim R, et al. PLoS One. 2013 Jun 17;8(6):e65257. doi: 10.1371/journal.pone.0065257. Print 2013. PLoS One. 2013. PMID: 23799002 Free PMC article.
• Caveolin-1 and accelerated host aging in the breast tumor microenvironment: chemoprevention with rapamycin, an mTOR inhibitor and anti-aging drug.
  Mercier I, Camacho J, Titchen K, Gonzales DM, Quann K, Bryant KG, Molchansky A, Milliman JN, Whitaker-Menezes D, Sotgia F, Jasmin JF, Schwarting R, Pestell RG, Blagosklonny MV, Lisanti MP. Mercier I, et al. Am J Pathol. 2012 Jul;181(1):278-93. doi: 10.1016/j.ajpath.2012.03.017. Epub 2012 Jun 13. Am J Pathol. 2012. PMID: 22698676 Free PMC article.
• Effects of Ginsenoside Rg1 on the Biological Behavior of Human Amnion-Derived Mesenchymal Stem/Stromal Cells (hAD-MSCs).
  Ling L, Shu H, Huang Y, Hou J, Hua Y. Ling L, et al. Stem Cells Int. 2023 Feb 15;2023:7074703. doi: 10.1155/2023/7074703. eCollection 2023. Stem Cells Int. 2023. PMID: 36845966 Free PMC article.
• LZTFL1 inhibits kidney tumor cell growth by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway.
  Lu J, Fu LM, Cao Y, Fang Y, Cao JZ, Pan YH, Cen JJ, Liang YP, Chen ZH, Wei JH, Huang Y, Mumin MA, Xu QH, Wang YH, Zhu JQ, Liang H, Wang Z, Deng Q, Chen W, Jin XH, Liu ZP, Luo JH. Lu J, et al. Oncogene. 2023 May;42(19):1543-1557. doi: 10.1038/s41388-023-02666-x. Epub 2023 Mar 25. Oncogene. 2023. PMID: 36966254 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal