Akt2 inhibition enables the forkhead transcription factor FoxO3a to have a repressive role in estrogen receptor alpha transcriptional activity in breast cancer cells.

Molecular and Cellular Biology
Catia MorelliSebastiano Andò

Abstract

Estrogen receptor alpha (ER) and the insulin-like growth factor I receptor (IGF-IR) pathways are engaged in a functional cross talk in breast cancer, promoting tumor progression and increased resistance to anticancer treatments and radiotherapy. Here, we introduce new mechanisms through which proteins of the IGF-I/IGF-IR signaling pathway may regulate ER function in the absence of ligand. Our results indicate that in ER-positive breast cancer cells, Akt2 modulates ER transcriptional activity at multiple levels, including (i) the regulation of ER expression and its nuclear retention and (ii) the activation of one of its downstream targets, the Forkhead transcription factor FoxO3a. FoxO3a colocalizes and coprecipitates with ER in the nucleus, where it binds to Forkhead-responsive sequences on the ER target pS2/TFF-1 promoter; in addition, FoxO3a silencing leads to an increase of ER transcriptional activity, suggesting a repressive role of the Forkhead transcription factor in ER function. Moreover, 17beta-estradiol upregulates FoxO3a levels, which could represent the basis for an ER-mediated homeostatic mechanism. These findings provide further evidence of the importance of mediators of the growth factor signaling in ER regulation...Continue Reading

References

Feb 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M BerryP Chambon
Oct 1, 1984·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·G M ClarkW L McGuire
Feb 12, 1998·The Journal of Biological Chemistry·M AndjelkovićB A Hemmings
Mar 6, 1999·Breast Cancer Research and Treatment·C K Osborne
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·T Improta-BrearsD P McDonnell
Jun 8, 1999·The Journal of Biological Chemistry·G RenaP Cohen
Jun 16, 1999·Endocrine Reviews·J F Couse, K S Korach
Dec 2, 1999·Experimental Cell Research·E S Kandel, N Hay
May 20, 2000·Journal of Mammary Gland Biology and Neoplasia·E AndersonA Howell
Jul 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·D K BiswasA B Pardee
Aug 30, 2000·Nature·C M PerouD Botstein
Dec 14, 2001·The Journal of Biological Chemistry·Ying ZhuKenneth K Wu
May 16, 2002·The Journal of Biological Chemistry·Ahmed A SamatarChandra C Kumar
Nov 14, 2002·The Journal of Steroid Biochemistry and Molecular Biology·Linda A deGraffenriedSuzanne A W Fuqua
Jan 17, 2003·Journal of the National Cancer Institute·Gottfried KonecnyDennis J Slamon
Jan 28, 2003·Cancer·Judith Clancy Keen, Nancy E Davidson
Feb 1, 2003·FEBS Letters·Abhijit Mazumdar, Rakesh Kumar
Mar 13, 2003·Breast Cancer Research : BCR·Olle StålLars Erik Rutqvist
Jul 8, 2003·The Journal of Pathology·Caroline J WittonJohn M S Bartlett
Jul 15, 2003·The Journal of Biological Chemistry·Frank M J JacobsMarten P Smidt
Sep 21, 2004·Breast Cancer Research and Treatment·Nicola J JordanRobert I Nicholson
Aug 3, 2006·Journal of Clinical Pathology·Diego SisciEva Surmacz

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Citations

Apr 8, 2010·The Journal of Biological Chemistry·William KongJin Q Cheng
Feb 5, 2014·Clinical & Experimental Metastasis·Hassan Fazilaty, Parvin Mehdipour
Mar 29, 2014·Journal of Cancer Research and Clinical Oncology·Nuiki Iota ChantziMuichael N Alexis
Jan 15, 2011·Journal of Cell Communication and Signaling·Tiziana GiraldiFerdinando Auricchio
Nov 28, 2015·Endocrine-related Cancer·Martyn Bullock
Aug 24, 2019·Nature Communications·Mohamed Osama Ali AbdallaNoriko Saitoh
Oct 20, 2015·Biomolecular Concepts·Maike Busch, Nicole Dünker
Jul 3, 2013·Microscopy Research and Technique·M Colitti, F Parillo
Nov 23, 2019·Cell Communication and Signaling : CCS·Nico Hinz, Manfred Jücker
Mar 11, 2018·Molecular Cancer Research : MCR·Michele PellegrinoDiego Sisci
Jun 29, 2011·Biochimica Et Biophysica Acta·Guri TzivionGopalakrishnan Ramakrishnan

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