Loss of PTEN function may account for reduced proliferation pathway sensitivity to LY294002 in human prostate and bladder cancer cells.

Journal of Cancer Research and Clinical Oncology
Shigeru KandaYasuyoshi Miyata

Abstract

Inhibition of phosphoinositide 3 (PI3)-kinase pathway is attractive for cancer treatment. To examine the role of the phosphatase and tensin homolog (PTEN) in the development of resistance to the treatment. We cultured human prostate cancer cells (DU145 and PC-3 cells) and bladder cancer cells (EJ-1 and UM-UC-3 cells) with a PI3-kinase inhibitor, LY294002 for more than 6 weeks and cell proliferation was studied. Activation of Akt1 and ERK was examined by immunoblotting. We introduced the wild type PTEN in UM-UC-3 cells and their proliferation along with the signaling pathways was also examined. After 6 weeks, proliferation pathway sensitivity to LY294002 was reduced in cells expressing PTEN, but not in PTEN-null cells. PD98059, a MAPK/ERK kinase inhibitor, significantly inhibited proliferation of PTEN-expressing cells, but not PTEN-null cells. Stable PTEN expression in PTEN-null UM-UC-3 cells increased serum-induced ERK activation and sensitivity to PD98059-treatment, and reduced sensitivity to LY294002 after 6 weeks of exposure. Loss of PTEN function may protect against resistance to PI3-kinase inhibitors through an addiction to the PI3-kinase/Akt pathway.

References

Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·D M Li, H Sun
Jun 9, 1999·British Journal of Cancer·J S AveyardM A Knowles
Nov 24, 1999·Journal of the National Cancer Institute·I U AliM Dean
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·B H JiangP K Vogt
Aug 16, 2001·Proceedings of the National Academy of Sciences of the United States of America·M S NeshatC L Sawyers
Sep 22, 2001·Endocrine-related Cancer·R C Stein
Jul 6, 2002·Science·I Bernard Weinstein
Jun 15, 2004·The Biochemical Journal·Nick R Leslie, C Peter Downes
Jun 24, 2004·Seminars in Cell & Developmental Biology·Julian Downward
Sep 16, 2004·Annals of Oncology : Official Journal of the European Society for Medical Oncology·L A DeGraffenriedM Hidalgo
Aug 3, 2005·Cancer Research·Shigeru KandaHiroshi Kanetake
Oct 14, 2005·Anti-cancer Drugs·Kashif A AhmadKhalil Ahmed
Dec 13, 2005·Nature Reviews. Cancer·Andreas G BaderPeter K Vogt
May 30, 2006·Biochemical and Biophysical Research Communications·Shigeru KandaYasuyoshi Miyata

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Citations

Jul 28, 2010·Laboratory Investigation; a Journal of Technical Methods and Pathology·Christina Barbara Ching, Donna Elizabeth Hansel
Jun 3, 2020·European Journal of Pharmacology·Milad AshrafizadehMasoud Najafi

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