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Raf‐1‐induced cell cycle arrest in LNCaP human prostate cancer cells
Author(s) -
Ravi Rajani K.,
McMahon Martin,
Yangang Zang,
Williams Jerry R.,
Dillehay Larry E.,
Nelkin Barry D.,
Mabry Mack
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19990315)72:4<458::aid-jcb2>3.0.co;2-c
Subject(s) - lncap , mapk/erk pathway , prostate cancer , cancer research , cell cycle , cell growth , cancer cell , chemistry , biology , microbiology and biotechnology , kinase , cell , cancer , biochemistry , genetics
Prostate cancer is the most commonly diagnosed neoplasm in men. LNCaP cells continue to possess many of the molecular characteristics of in situ prostate cancer. These cells lack ras mutations, and mitogen‐activated protein kinase (MAPK) is not extensively phosphorylated in these cells. To determine the effects of ras/raf/MAPK pathway activation in these cells, we transfected LNCaP cells with an activatable form of c‐raf‐1(ΔRaf‐1:ER). Activation of ΔRaf‐1:ER, with resultant MAPK activation, reduced plating efficiency and soft agarose cloning efficiency 30‐fold in LNCaP cells. Cell cycle distribution showed an accumulation of cells in G1 and was associated with the induction of CDK inhibitor p21 WAF1/CIP1 at the protein and mRNA levels. p21 WAF1/CIP1 mRNA stability was increased after ΔRaf‐1:ER activation. In addition, activated ΔRaf‐1:ER induced the senescence associated‐β‐galactosidase in LNCaP cells. These data demonstrate that raf activation can activate growth inhibitory pathways leading to growth suppression in prostate carcinoma cells and also suggest that raf/MEK/MAPK pathway activation, rather than inhibition, may be a therapeutic target for some human prostate cancer cells. J. Cell. Biochem. 72:458–469, 1999. © 1999 Wiley‐Liss, Inc.