title: HOXB13-mediated suppression of p21WAF1/CIP1 regulates JNK/c-Jun signaling in prostate cancer cells.
abstract: Many prostate cancer (PCa) patients die of recurrent disease due to the emergence of hormone-independent cancer cells of which the mechanism is not fully understood. Our previous studies demonstrated that most castration- resistant prostate cancers (CRPC) overexpress the HOXB13 transcription factor to confer positive growth signals. Since HOXB13 also suppresses p21WAF1/CIP1 (p21) expression, we studied the correlation between HOXB13 and p21 in selected samples of PCa. While there was no statistically significant correlation between expression of HOXB13 and p21, HOXB13-deficient tumors had three times higher odds for expressing p21 than HOXB13-positive tumors. Moreover, CRPC showed more negative correlation than hormone-dependent PCa (HDPC). Further in vitro proliferation assay demonstrated that androgen did not affect the growth-suppressive function of p21 in androgen-dependent PCa cells, suggesting that p21 seems to override the growth-promoting function of androgen and suppression of p21 expression by HOXB13 is an important step in PCa cell survival under no androgen influence. HOXB13 also inhibited AP-1 signals via suppressed expression of JNK/c-Jun. While HOXB13 suppressed p21 expression via regulation of JNK signals, alteration of p21 expression also affected c-Jun and AP-1 activity. Taken together, overexpression of HOXB13 in CRPC is an important step in avoiding the growth-suppressive effect of p21 in a harsh condition such as an androgen-deprived environment.
authors.affiliation: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Young-Rang
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Urology, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Taek Won
authors.initials: TW
authors.lastname: Kang
authors.affiliation: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Phuong Kim
authors.initials: PK
authors.lastname: To
authors.affiliation: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Nguyen Thi
authors.initials: NT
authors.lastname: Xuan Nguyen
authors.affiliation: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Chaeyong
authors.initials: C
authors.lastname: Jung
authors.affiliation: Department of Statistics, College of Natural Sciences, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D000728:Androgens; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C484414:HOXB13 protein, human; D018398:Homeodomain Proteins