Increased constitutive activity of PKB/Akt in tamoxifen resistant breast cancer MCF-7 cells

Breast Cancer Research and Treatment
Nicola JordanRobert I Nicholson

Abstract

The tamoxifen-resistant (TAM-R) MCF-7 breast cancer cell line has been used as a model to identify the signalling pathways that enable resistant cancer cells to grow independently of steroid hormones. In TAM-R cells, peptide growth factor signalling pathways appear to be important in modified cell behaviour, growth and survival. The PI3 kinase signalling components Akt1 and Akt2 are expressed at similar levels by both parental wild-type MCF-7 and TAM-R cells, but Akt1 phosphorylation is significantly increased in TAM-R cells grown under basal conditions. High levels of basal Akt, GSK3 alpha / beta and p70S6 kinase phosphorylation are all inhibited by the PI3 kinase inhibitor, LY 294002. The ligands for the EGFR/erbB1 receptor, EGF (epidermal growth factor) and TGF alpha (transforming growth factor- alpha ) demonstrate an increased ability to activate Akt in TAM-R compared with parental MCF-7 cells and it is proposed that the preferred autocrine or paracrine activation of Akt occurs via the erbB heterodimer EGFR/erbB2 in TAM-R cells. Akt phosphorylation is reduced by gefitinib ("Iressa"/ZD1839). The results suggest that the PI3 kinase pathway plays a role in proliferation of TAM-R cells and is important in the increased EGF indu...Continue Reading

References

Oct 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J Q ChengJ R Testa
Jan 1, 1991·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M ToiT Toge
Jul 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·S P Staal
Jun 1, 1994·Molecular and Cellular Biology·S P SoltoffL C Cantley
Aug 22, 1995·International Journal of Cancer. Journal International Du Cancer·A BellacosaJ R Testa
Jan 1, 1994·Breast Cancer Research and Treatment·R I NicholsonR W Blamey
Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·J Q ChengJ R Testa
Aug 1, 1996·Cytokine & Growth Factor Reviews·V RuschE Dmitrovsky
Dec 31, 1997·The Journal of Biological Chemistry·R MeierB A Hemmings
Feb 12, 1998·The Journal of Biological Chemistry·M AndjelkovićB A Hemmings
Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·Y E WhangC L Sawyers
Aug 26, 1998·Molecular and Cellular Biology·M A OlayioyeN E Hynes
Jul 15, 1999·The International Journal of Biochemistry & Cell Biology·A Wells
Aug 12, 1999·Biochemical and Biophysical Research Communications·W LiuR A Roth
Dec 2, 1999·Experimental Cell Research·E S Kandel, N Hay
Mar 14, 2000·The Journal of Biological Chemistry·B P ZhouM C Hung
Aug 5, 2000·International Journal of Cancer. Journal International Du Cancer·A deFazioR L Sutherland
Sep 5, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·D KimJ Chung
Mar 1, 2002·British Journal of Cancer·G Pérez-TenorioUNKNOWN Southeast Sweden Breast Cancer Group
Aug 9, 2002·Molecular and Cellular Biology·Michael P ScheidJames R Woodgett
Aug 23, 2002·Pharmacology & Therapeutics·Michelle M Hill, Brian A Hemmings
Sep 24, 2002·Nature Medicine·Jiyong LiangJoyce M Slingerland
Mar 13, 2003·Breast Cancer Research : BCR·Olle StålLars Erik Rutqvist
Jun 28, 2003·FEBS Letters·Michael P Scheid, James R Woodgett
Jan 22, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert I NicholsonJulia M W Gee

❮ Previous
Next ❯

Citations

Oct 15, 2005·Bulletin of Experimental Biology and Medicine·A M ShcherbakovN E Kushlinskii
Oct 19, 2013·Bulletin of Experimental Biology and Medicine·A M ScherbakovN E Kushlinskii
Oct 26, 2005·Breast Cancer Research and Treatment·Robert I Nicholson, Stephen R Johnston
Oct 26, 2005·Breast Cancer Research and Treatment·Mitch DowsettRichard J Pietras
Sep 28, 2006·Breast Cancer Research and Treatment·Elizabeth CanningsJohn M S Bartlett
Nov 17, 2009·Breast Cancer Research and Treatment·Atanas IgnatovThomas Kalinski
Dec 21, 2010·Breast Cancer Research and Treatment·Nguyen Thi Thuy PhuongKeon Wook Kang
May 9, 2007·Reviews in Endocrine & Metabolic Disorders·R I NicholsonJ M W Gee
Aug 10, 2007·Breast Cancer Research : BCR·Iain R HutchesonRobert I Nicholson
Sep 6, 2012·Endocrine Reviews·Bramanandam ManavathiRakesh Kumar
Jul 5, 2006·Biological & Pharmaceutical Bulletin·Yunyu Zhao, Liguang Lou
Mar 4, 2011·Endocrine-related Cancer·Chellappagounder ThangavelErik S Knudsen
Apr 30, 2013·Endocrine-related Cancer·Per Eystein Lønning, Hans Petter Eikesdal
Jan 23, 2014·Acta Biochimica Et Biophysica Sinica·Youngseok LeeBolin Liu
Jan 23, 2014·Journal of Translational Medicine·Yu GuLisong Teng
Apr 7, 2009·Cell Communication & Adhesion·P Raaj KhusialGary S Goldberg
Dec 19, 2015·Journal of Medicinal Chemistry·Rui XiongGregory Rj Thatcher
Nov 29, 2015·Bioorganic & Medicinal Chemistry·Rodrigo Mendoza-SanchezJames L Gleason
Sep 23, 2008·Biochimica Et Biophysica Acta·Marinella ZilliUNKNOWN Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO)
Apr 29, 2015·Molecular and Cellular Endocrinology·Zhao-Yi Wang, Li Yin
Aug 10, 2005·The Journal of Pathology·Tove KirkegaardJohn M S Bartlett
Sep 23, 2008·International Journal of Cancer. Journal International Du Cancer·Tiziana ServideiRiccardo Riccardi
Feb 3, 2007·International Journal of Cancer. Journal International Du Cancer·Bolin LiuAnn D Thor
Sep 10, 2009·International Journal of Cancer. Journal International Du Cancer·Eleanor GutteridgeJulia Gee

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Breast Cancer: Chemo-Resistance

Some cancers are difficult to treat and aggressive including the "triple-negative" breast cancer. This type of cancer is chemoresistant even before chemotherapy begins. Here are the latest discoveries chemo-resistance in breast cancer.