HOXB13-mediated suppression of p21WAF1/CIP1 regulates JNK/c-Jun signaling in prostate cancer cells

Kim,Young-Rang; Kang,Taek  Won; To,Phuong  Kim; Xuan Nguyen,Nguyen  Thi; Cho,Young  Seok; Jung,Chaeyong; Kim,Min  Soo

doi:10.3892/or.2016.4563

HOXB13-mediated suppression of p21WAF1/CIP1 regulates JNK/c-Jun signaling in prostate cancer cells

Authors:
- Young-Rang Kim
- Taek Won Kang
- Phuong Kim To
- Nguyen Thi Xuan Nguyen
- Young Seok Cho
- Chaeyong Jung
- Min Soo Kim
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Affiliations: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea, Department of Urology, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea, Department of Statistics, College of Natural Sciences, Chonnam National University, Gwangju 500-757, Republic of Korea
Published online on: January 15, 2016 https://doi.org/10.3892/or.2016.4563
Pages: 2011-2016

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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.

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