Role of PI3K signaling in survival and progression of LNCaP prostate cancer cells to the androgen refractory state

Endocrinology
H MurilloD J Tindall

Abstract

The mechanisms by which prostate cancer (PCa) cells progress to a hormone refractory state are poorly understood. The progression process under androgen ablation conditions involves the survival of at least a portion of malignant cells and their eventual proliferation in an androgen-independent manner. The goal of this study was to investigate the role of PI3K signaling in such a progression. Using an in vitro model of androgen ablation, we show that after removal of androgen support, the human PCa cell line LNCaP initially arrested in G(1) and trans-differentiated into neuroendocrine-like cells that eventually resumed androgen-independent proliferation. Both acute and chronic androgen ablation resulted in an increase in basal levels of PI3K and Akt activity, which were sustained throughout the progression process. Under these conditions, inhibition of PI3K, pharmacologically or with ectopic expression of PTEN, arrested cell proliferation and blocked progression to the androgen-independent state. In contrast, LNCaP cells in the presence of androgens were marginally sensitive to PI3K inhibition. During the chronic stage of androgen deprivation, androgen-independent proliferation correlated with diminished p27(kip1) protein level...Continue Reading

Citations

Sep 29, 2011·Asian Journal of Andrology·Paramita M Ghosh
Jul 9, 2009·The Journal of Biological Chemistry·Michael R EpisPeter J Leedman
Sep 30, 2010·The Journal of Biological Chemistry·Yan DingMary E Choi
Apr 15, 2011·The Journal of Biological Chemistry·James Robert Krycer, Andrew John Brown
Apr 26, 2012·Carcinogenesis·Kangdong LiuZigang Dong
Sep 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wen-Chin HuangLeland W K Chung
Mar 19, 2005·The Journal of Clinical Investigation·Liyan ZhuangMichael R Freeman
May 1, 2010·Therapeutic Advances in Medical Oncology·Joaquim Bellmunt, William K Oh
Jan 9, 2004·Reproductive Biology and Endocrinology : RB&E·Delisha A StewartRobert A Sikes
Dec 19, 2003·Breast Cancer Research : BCR·Angel Alkarain, Joyce Slingerland
Jan 24, 2009·Molecular Endocrinology·Hannelore V HeemersDonald J Tindall
Mar 30, 2012·Molecular Endocrinology·Lucy J SchmidtHannelore V Heemers
Jul 31, 2013·International Journal of Molecular Sciences·Takashi KobayashiOsamu Ogawa
May 23, 2012·International Journal of Oncology·Rachel M SquillaceVictor M Rivera
Mar 25, 2006·Future Oncology·Haojie Huang, Donald J Tindall
Jan 30, 2013·Biochimica Et Biophysica Acta·James Robert Krycer, Andrew John Brown
Jan 15, 2014·Cancer Metastasis Reviews·Jennifer Wu, Evan Yu
Jan 22, 2014·Cancer Metastasis Reviews·Lei ChangYong Li
Aug 17, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Liqun ChenParamita M Ghosh
Oct 23, 2012·Clinical Genitourinary Cancer·Connor HallMin H Kang
Apr 12, 2011·Biochemical Pharmacology·A-Mei HuangYeong-Shiau Pu
Sep 10, 2010·Biochimica Et Biophysica Acta·Sathish Srinivasan, Zafar Nawaz
Apr 15, 2006·Genes, Chromosomes & Cancer·Horacio MurilloDonald J Tindall
Feb 3, 2009·International Journal of Urology : Official Journal of the Japanese Urological Association·Satoko KojimaYuzo Furuya

❮ 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.