Premium
Mitogen‐activated protein kinase pathway is involved in androgen‐independent PSA gene expression in LNCaP cells
Author(s) -
Franco Omar E.,
Onishi Takehisa,
Yamakawa Kensuke,
Arima Kiminobu,
Yanagawa Makoto,
Sugimura Yoshiki,
Kawamura Juichi
Publication year - 2003
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.10258
Subject(s) - lncap , androgen , transfection , electrophoretic mobility shift assay , biology , microbiology and biotechnology , protein kinase a , expression vector , prostate cancer , gene expression , reporter gene , cancer research , kinase , gene , endocrinology , hormone , cancer , genetics , recombinant dna
BACKGROUND Prostate specific antigen (PSA) is regulated by growth factors and hormones through functional androgen responsive elements in the promoter region of the PSA gene. However, the molecular basis for androgen independent PSA elevation in hormone refractory prostate cancer is unknown. The purpose of this study was to investigate the role of MAP kinase activation in androgen independent regulation of PSA expression. METHODS LNCaP cells transfected with MEK1 expression vector with or without the MAP kinase inhibitor U0126 under low androgen conditions were analyzed by luciferase assay and electrophoretic mobility shift assay (EMSA). RESULTS Transfection experiments of the proximal PSA promoter linked to Luc‐reporter identified one region designated as “B” motif centered at −60 bp to be essential for basal activation. Co‐transfection with the MEK1 activated vector enhanced PSA expression, while mutation of the “B” motif totally abrogated this induction. EMSA showed a specific DNA–protein complex, but Sp1 family members and AR do not interact with the “B” region by supershift analysis. CONCLUSIONS Our data suggest that enhanced androgen‐independent PSA gene expression in MAP kinase‐induced LNCaP cells is mediated, at least in part, by the “B” motif of the PSA promoter. Prostate 56: 319–325, 2003. © 2003 Wiley‐Liss, Inc.