HOXB13 promotes androgen independent growth of LNCaP prostate cancer cells by the activation of E2F signaling

Molecular Cancer

Research

Ra-Young Park¹  Young-Rang Kim¹  Nguyen Thi Xuan¹  Kyu Youn Ahn²  Kwang Il Nam²  Chaeyong Jung²  Chan Choi³  Min Soo Kim⁴  Kyung-Jin Oh⁵  Taek-Won Kang⁶  Dong-Deuk Kwon⁶ 

[1] Department of Anatomy, Chonnam National University Medical School, Gwangju, Korea;Department of Anatomy, Chonnam National University Medical School, Gwangju, Korea;Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea;Department of Pathology, Chonnam National University Medical School, Gwangju, Korea;Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea;Department of Statistics, Chonnam National University, Gwangju, Korea;Department of Urology, Chonnam National University Medical School, Gwangju, Korea;Department of Urology, Chonnam National University Medical School, Gwangju, Korea;Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea;

关键词: Androgen;    Androgen Receptor;    Prostate Cancer Cell;    LNCaP Cell;    LNCaP Prostate Cancer Cell;   

DOI  :  10.1186/1476-4598-9-124

 received in 2010-02-24, accepted in 2010-05-27,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundAndrogen signaling plays a critical role in the development of prostate cancer and its progression. However, androgen-independent prostate cancer cells emerge after hormone ablation therapy, resulting in significant clinical problems. We have previously demonstrated that the HOXB13 homeodomain protein functions as a prostate cancer cell growth suppressor by inhibiting androgen-mediated signals. However, the role of the HOXB13 in androgen-independent growth of prostate cancer cells remains unexplained.ResultsIn this report, we first demonstrated that HOXB13 was highly overexpressed in hormone-refractory tumors compared to tumors without prostate-specific antigen after initial treatment. Functionally, in an androgen-free environment minimal induction of HOXB13 in LNCaP prostate cancer cells, to the level of the normal prostate, markedly promoted cell proliferation while suppression inhibited cell proliferation. The HOXB13-mediated cell growth promotion in the absence of androgen, appears to be mainly accomplished through the activation of RB-E2F signaling by inhibiting the expression of the p21waf tumor suppressor. Indeed, forced expression of HOXB13 dramatically decreased expression of p21waf; this inhibition largely affected HOXB13-mediated promotion of E2F signaling.ConclusionsTaken together, the results of this study demonstrated the presence of a novel pathway that helps understand androgen-independent survival of prostate cancer cells. These findings suggest that upregulation of HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling.

【 授权许可】

Unknown   
© Kim et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.