Molecular alterations associated with LNCaP cell progression to androgen independence

Xu Bao Shi, Ai Hong Ma, Clifford G. Tepper, Liang Xia, Jeffrey P. Gregg, Regina Gandour-Edwards, Philip C. Mack, Hsing Jien Kung, Ralph W. DeVere White

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

BACKGROUND. There is no effective therapy currently available for androgen-independent (AI) prostate cancer (CaP). This is largely due to lack of information about the molecular mechanisms by which androgen-dependent tumor cells progress to androgen independence. In this study, we investigated molecular alterations occurring in AI LNCaP cells. METHODS. We established and characterized three AI LNCaP sublines that exhibited a wide range of cytogenetic alterations. In order to understand why androgen-sensitive LNCaP cells can survive in an androgen-deprived environment, we analyzed the expression of signaling proteins associated with proliferation and survival of AI cells. In addition, gene expression profiling was performed to gain insight into molecular alterations in these LNCaP sublines. RESULTS. These LNCaP sublines exhibited heightened levels of androgen receptor (AR), HER2, MAPK, serine 473-phosphorylated Akt, and Bcl-2, implicating these proteins as mediators of AI growth. Gene expression profiling identified a common set of 66 genes that were differentially expressed in all three sublines compared to the parental LNCaP cells. Of these, 32 were apparently androgen regulated, while the remainder comprised an expression signature specific for androgen independence. CONCLUSION. We have developed AI LNCaP cell models and identified several genes that are specifically expressed in these models. Elucidating the relative importance of these genetic changes will help define the molecular mechanism by which CaP progresses to androgen independence.

Original languageEnglish
Pages (from-to)257-271
Number of pages15
JournalProstate
Volume60
Issue number3
DOIs
Publication statusPublished - Aug 1 2004
Externally publishedYes

Keywords

  • Androgen independence
  • Androgen receptor
  • Microarray
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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  • Cite this

    Shi, X. B., Ma, A. H., Tepper, C. G., Xia, L., Gregg, J. P., Gandour-Edwards, R., Mack, P. C., Kung, H. J., & DeVere White, R. W. (2004). Molecular alterations associated with LNCaP cell progression to androgen independence. Prostate, 60(3), 257-271. https://doi.org/10.1002/pros.20039