Bcl-xL is overexpressed in hormone-resistant prostate cancer and promotes survival of LNCaP cells via interaction with proapoptotic Bak

Endocrinology. 2006 Oct;147(10):4960-7. doi: 10.1210/en.2006-0502. Epub 2006 Jun 22.


Androgen-sensitive prostate cancer cells turn androgen resistant through complex mechanisms that involve dysregulation of apoptosis. We investigated the role of antiapoptotic Bcl-xL in the progression of prostate cancer as well as the interactions of Bcl-xL with proapoptotic Bax and Bak in androgen-dependent and -independent prostate cancer cells. Immunohistochemical analysis was used to study the expression of Bcl-xL in a series of 139 prostate carcinomas and its association with Gleason grade and time to hormone resistance. Expression of Bcl-xL was more abundant in prostate carcinomas of higher Gleason grades and significantly associated with the onset of hormone-refractory disease. In vivo interactions of Bcl-xL with Bax or Bak in untreated and camptothecin-treated LNCaP and PC3 cells were investigated by means of coimmunoprecipitation. In the absence of any stimuli, Bcl-xL interacts with Bax and Bak in androgen-independent PC3 cells but only with Bak in androgen-dependent LNCaP cells. Interactions of Bcl-xL with Bax and Bak were also evidenced in lysates from high-grade prostate cancer tissues. In LNCaP cells treated with camptothecin, an inhibitor of topoisomerase I, the interaction between Bcl-xL and Bak was absent after 36 h, Bcl-xL decreased gradually and Bak increased coincidentally with the progress of apoptosis. These results support a model in which Bcl-xL would exert an inhibitory effect over Bak via heterodimerization. We propose that these interactions may provide mechanisms for suppressing the activity of proapoptotic Bax and Bak in prostate cancer cells and that Bcl-xL expression contributes to androgen resistance and progression of prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / genetics*
  • Blotting, Western
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • Male
  • Phenotype
  • Prostatic Neoplasms / genetics*
  • bcl-2 Homologous Antagonist-Killer Protein / biosynthesis
  • bcl-2 Homologous Antagonist-Killer Protein / genetics*
  • bcl-2-Associated X Protein / genetics
  • bcl-X Protein / genetics*


  • Antineoplastic Agents, Hormonal
  • Antineoplastic Agents, Phytogenic
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Camptothecin