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Possible role of adaptive mutation in resistance to antiandrogen in prostate cancer cells
Author(s) -
Hara Takahito,
Kouno Jin,
Nakamura Kazuyo,
Kusaka Masami,
Yamaoka Masuo
Publication year - 2005
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20282
Subject(s) - bicalutamide , lncap , antiandrogen , prostate cancer , cancer research , androgen receptor , androgen , biology , endocrinology , medicine , cancer , genetics , hormone
BACKGROUND Some mutations of androgen receptor (AR) confer resistance to antiandrogen to prostate cancer (PC) cells. Previously we reported that LNCaP‐cxD2 cells established from androgen‐dependent LNCaP‐FGC PC cells as an antiandrogen bicalutamide‐resistant subline harbor W741C/L mutation in the AR gene. In this report, we examined one possible mechanism of the resistance. METHODS Change in the gene expression and the protein levels relevant to mutagenesis in LNCaP‐FGC cells during bicalutamide‐treatment was assessed. The AR sequence of bicalutamide‐resistant LNCaP‐cxD2 cells was compared with that of parental LNCaP‐FGC cells. RESULTS The expression of DNA polymerases (Pol) switched from high‐fidelity subset to error‐prone subset, and DNA mismatch repair proteins (MMR) were down‐regulated. The rate of multiple mutations in the AR gene was higher in LNCaP‐cxD2 cells than LNCaP‐FGC cells. CONCLUSIONS These results suggest the hypermutational state might occur in LNCaP‐FGC cells during bicalutamide‐treatment, which might create the W741C/L mutant AR leading to bicalutamide‐resistance. Prostate. © 2005 Wiley‐Liss, Inc.