The oncogenic potential of a prostate cancer-derived androgen receptor mutant

Xu Bao Shi, Lingru Xue, Clifford G. Tepper, Regina Gandour-Edwards, Paramita Ghosh, Hsing Jien Kung, Ralph W. DeVere White

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

BACKGROUND. The role of androgen receptor (AR) mutations in the initiation of prostate cancer (CaP) remains unclear. The purpose of this study was to assess the influence of an AR mutation on prostate tumorigenesis and to determine the resulting molecular alterations. METHODS. Wild-type AR (AR WT) or the CaP-derived K580R AR (ARK580R) mutant was stably transfected into SV40-immortalized human prostate epithelial pRNS-1-1 cells that lack AR expression and fail to grow in nude mice. The ability of these AR-transfected cell lines to form tumor was investigated in vitro and in vivo. Additionally, gene expression profiling of these cell lines was performed. RESULTS. Compared with the ARWT, the ARK580R induced greater than sixfold increase in colony formation in soft agar. In vivo studies confirmed that the ARK580R-transfected pRNS-1-1 cells were able to form tumors in nude mice. Using a combination of microarray and RT-PCR, 29 differentially expressed genes were identified in ARK580R cells. It was found that silencing the expression of placental alkaline phosphatase (ALPP) that was upregulated in ARK580R cells resulted in significant inhibition of cell growth. Furthermore, the ARK580R-transfected pRNS-1-1 cells expressed markedly increased p-Akt and p-p70 S6K. CONCLUSION. The ARK580R mutation promoted the malignant transformation of prostate epithelial cells. This was associated with upregulation of ALPP and subsequent activation of the Akt signaling pathway.

Original languageEnglish
Pages (from-to)591-602
Number of pages12
JournalProstate
Volume67
Issue number6
DOIs
Publication statusPublished - May 1 2007
Externally publishedYes

Fingerprint

Androgen Receptors
Prostatic Neoplasms
Prostate
Nude Mice
Mutation
Cell Line
Gene Expression Profiling
Agar
Alkaline Phosphatase
Neoplasms
Carcinogenesis
Up-Regulation
Epithelial Cells
Polymerase Chain Reaction
Growth
Genes

Keywords

  • Androgen receptor mutation
  • Prostate cancer
  • Tumorigenesis

ASJC Scopus subject areas

  • Urology

Cite this

Shi, X. B., Xue, L., Tepper, C. G., Gandour-Edwards, R., Ghosh, P., Kung, H. J., & DeVere White, R. W. (2007). The oncogenic potential of a prostate cancer-derived androgen receptor mutant. Prostate, 67(6), 591-602. https://doi.org/10.1002/pros.20544

The oncogenic potential of a prostate cancer-derived androgen receptor mutant. / Shi, Xu Bao; Xue, Lingru; Tepper, Clifford G.; Gandour-Edwards, Regina; Ghosh, Paramita; Kung, Hsing Jien; DeVere White, Ralph W.

In: Prostate, Vol. 67, No. 6, 01.05.2007, p. 591-602.

Research output: Contribution to journalArticle

Shi, XB, Xue, L, Tepper, CG, Gandour-Edwards, R, Ghosh, P, Kung, HJ & DeVere White, RW 2007, 'The oncogenic potential of a prostate cancer-derived androgen receptor mutant', Prostate, vol. 67, no. 6, pp. 591-602. https://doi.org/10.1002/pros.20544
Shi XB, Xue L, Tepper CG, Gandour-Edwards R, Ghosh P, Kung HJ et al. The oncogenic potential of a prostate cancer-derived androgen receptor mutant. Prostate. 2007 May 1;67(6):591-602. https://doi.org/10.1002/pros.20544
Shi, Xu Bao ; Xue, Lingru ; Tepper, Clifford G. ; Gandour-Edwards, Regina ; Ghosh, Paramita ; Kung, Hsing Jien ; DeVere White, Ralph W. / The oncogenic potential of a prostate cancer-derived androgen receptor mutant. In: Prostate. 2007 ; Vol. 67, No. 6. pp. 591-602.
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N2 - BACKGROUND. The role of androgen receptor (AR) mutations in the initiation of prostate cancer (CaP) remains unclear. The purpose of this study was to assess the influence of an AR mutation on prostate tumorigenesis and to determine the resulting molecular alterations. METHODS. Wild-type AR (AR WT) or the CaP-derived K580R AR (ARK580R) mutant was stably transfected into SV40-immortalized human prostate epithelial pRNS-1-1 cells that lack AR expression and fail to grow in nude mice. The ability of these AR-transfected cell lines to form tumor was investigated in vitro and in vivo. Additionally, gene expression profiling of these cell lines was performed. RESULTS. Compared with the ARWT, the ARK580R induced greater than sixfold increase in colony formation in soft agar. In vivo studies confirmed that the ARK580R-transfected pRNS-1-1 cells were able to form tumors in nude mice. Using a combination of microarray and RT-PCR, 29 differentially expressed genes were identified in ARK580R cells. It was found that silencing the expression of placental alkaline phosphatase (ALPP) that was upregulated in ARK580R cells resulted in significant inhibition of cell growth. Furthermore, the ARK580R-transfected pRNS-1-1 cells expressed markedly increased p-Akt and p-p70 S6K. CONCLUSION. The ARK580R mutation promoted the malignant transformation of prostate epithelial cells. This was associated with upregulation of ALPP and subsequent activation of the Akt signaling pathway.

AB - BACKGROUND. The role of androgen receptor (AR) mutations in the initiation of prostate cancer (CaP) remains unclear. The purpose of this study was to assess the influence of an AR mutation on prostate tumorigenesis and to determine the resulting molecular alterations. METHODS. Wild-type AR (AR WT) or the CaP-derived K580R AR (ARK580R) mutant was stably transfected into SV40-immortalized human prostate epithelial pRNS-1-1 cells that lack AR expression and fail to grow in nude mice. The ability of these AR-transfected cell lines to form tumor was investigated in vitro and in vivo. Additionally, gene expression profiling of these cell lines was performed. RESULTS. Compared with the ARWT, the ARK580R induced greater than sixfold increase in colony formation in soft agar. In vivo studies confirmed that the ARK580R-transfected pRNS-1-1 cells were able to form tumors in nude mice. Using a combination of microarray and RT-PCR, 29 differentially expressed genes were identified in ARK580R cells. It was found that silencing the expression of placental alkaline phosphatase (ALPP) that was upregulated in ARK580R cells resulted in significant inhibition of cell growth. Furthermore, the ARK580R-transfected pRNS-1-1 cells expressed markedly increased p-Akt and p-p70 S6K. CONCLUSION. The ARK580R mutation promoted the malignant transformation of prostate epithelial cells. This was associated with upregulation of ALPP and subsequent activation of the Akt signaling pathway.

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