E2F1 inhibits c-Myc-driven apoptosis via PIK3CA/Akt/mTOR and COX-2 in a mouse model of human liver cancer.

Gastroenterology
Sara LaduSnorri S Thorgeirsson

Abstract

Resistance to apoptosis is essential for cancer growth. We previously reported that hepatic coexpression of c-Myc and E2F1, 2 key regulators of proliferation and apoptosis, enhanced hepatocellular carcinoma (HCC) development in transgenic mice. Here, we investigated the molecular mechanisms underlying oncogenic cooperation between c-Myc and E2F1 in relationship to human liver cancer. Activation of pro- and antiapoptotic cascades was assessed by immunoblotting in experimental HCC models and in human HCC. Effect of antisense oligodeoxy nucleotides against c-Myc and E2F1 was studied in human HCC cell lines. Suppression of catalytic subunit p110alpha of phosphatidylinositol 3-kinase (PIK3CA)/Akt, mammalian target of rapamycin (mTOR), and cyclooxygenase (COX)-2 pathways was achieved by pharmacologic inhibitors and small interfering RNA in human and mouse HCC cell lines. Coexpression with E2F1 did not increase proliferation triggered by c-Myc overexpression but conferred a strong resistance to c-Myc-initiated apoptosis via concomitant induction of PIK3CA/Akt/mTOR and c-Myb/COX-2 survival pathways. COX-2 was not induced in c-Myc and rarely in E2F1 tumors. In human HCC, PIK3CA/Akt/mTOR and c-Myb/COX-2 pathways were similarly activated,...Continue Reading

Citations

Oct 1, 2011·Apoptosis : an International Journal on Programmed Cell Death·Gang ChenYi-Fang Zhao
Apr 28, 2012·Science Translational Medicine·Hala Elnakat ThomasSara C Kozma
Mar 10, 2010·Molecular Endocrinology·Zhipeng MengWendong Huang
Feb 2, 2011·PloS One·Sebastian RealAlbert Tauler
Jul 7, 2011·PloS One·Hussein Hassan AlyTsukasa Seya
Oct 14, 2011·Future Oncology·Qian ZhouWinnie Yeo
Feb 6, 2009·World Journal of Gastroenterology : WJG·Isabel Fabregat
Aug 12, 2014·World Journal of Gastroenterology : WJG·Konstantinos EvangelouAthanassios Kotsinas
Jun 19, 2012·Annual Review of Genomics and Human Genetics·Ze-Guang Han
Oct 16, 2015·The Journal of Cell Biology·Zhipeng ZouXiaochun Bai
Jul 16, 2009·Molecular Carcinogenesis·Carolin SchildGünter Schneider
Feb 15, 2013·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Deepak JoshiVaruna Aluvihare
Oct 30, 2015·Nature Communications·Boshi WangYongzhong Liu
Oct 1, 2009·The FEBS Journal·Elisabeth A CorcelleMarja Jäättelä
Mar 28, 2012·Virchows Archiv : an International Journal of Pathology·Marina PalaiologouDina G Tiniakos
Oct 16, 2012·Molecular Carcinogenesis·Kelly A Brant, George D Leikauf
Aug 29, 2020·Cells·Neeraj ChauhanMurali M Yallapu
Jun 16, 2015·World Journal of Gastroenterology : WJG·Madhusudana Girija Sanal
May 1, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Lorenzo AzzaliniRamón Bataller
Sep 19, 2014·Journal of Veterinary Internal Medicine·M CamposJ A Mol
Jun 3, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hussein Hassan AlyMakoto Hijikata
Mar 20, 2013·FEBS Letters·Li-Jun MiaoJing Wang
Apr 1, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jie LiJianmin Luo
Jan 21, 2017·Endocrine-related Cancer·Maria Santa RoccaAlberto Ferlin
Feb 26, 2020·Cancers·Manali Dimri, Ande Satyanarayana
Apr 2, 2011·The Journal of Biological Chemistry·Altaf A DarMohammed Kashani-Sabet
Jan 11, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lei ZhanBing Wei

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