Suppression of human prostate cancer cell growth by forced expression of connexin genes

Parmender P Mehta, Carlos Perez-Stable, Mehrdad Nadji, Mohsin Mian, Kamlesh Asotra, Bernard A. Roos

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

The cell-to-cell channels in gap junctions, formed of proteins called connexins (Cxs), provide a direct intercellular pathway for the passage of small signaling molecules [≤1 kD) between the cytoplasmic interiors of adjoining cells. It has been proposed that alteration in the expression and function of Cxs may be one of the genetic changes involved in the initiation of neoplasia. To elucidate the role of Cxs in the pathogenesis of human prostate cancer (PCA), the pattern of expression of Cx α1 (Cx43) and Cx β1 [Cx32) was studied by immunocytochemical analysis in normal prostate and in prostate tumors of different histological grades. While normal prostate epithelial cells expressed only Cxβ1, both Cxα1 and Cxβ1 were detected in PCA cells. The Cxs were localized at the cell-cell contact areas in normal prostate and well-differentiated prostate tumors; however, as prostate tumors progressed to more undifferentiated stages, the Cxs were localized in the cytoplasm, followed by an eventual loss in advanced stages. Thus, epithelial cells from prostate tumors showed subtle and gross alterations with regard to expression of Cx α1 and Cx β1 and their assembly into gap junctions during the progression of PCA. Retroviral-mediated transfer of Cx α1 and Cx β1 into a Cx-deficient human PCA cell line, LNCaP, inhibited growth, retarded tumorigenicity, and induced differentiation, and these effects were contingent upon the formation of gap junctions. In addition, the capacity to form gap junctions in most Cx-transduced LNCaP cells was lost upon serial passage. Taken together, these findings indicate that the control of proliferation and differentiation of epithelial cells in prostate tumors may depend on the appropriate assembly of Cx β1 and Cx α1 into gap junctions and that the development of PCA may involve the positive selection of cells with an impaired ability to form gap junctions.

Original languageEnglish (US)
Pages (from-to)91-110
Number of pages20
JournalDevelopmental Genetics
Volume24
Issue number1-2
StatePublished - Mar 16 1999

Fingerprint

Connexins
Prostate
Prostatic Neoplasms
Gap Junctions
Gene Expression
Growth
Neoplasms
Epithelial Cells
Serial Passage
Connexin 43
Cytoplasm
Cell Line

Keywords

  • Connexin32 (β connexin)
  • Connexin43 (α connexin)
  • Gap junctions
  • Intercellular communication
  • Prostate cancer

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Mehta, P. P., Perez-Stable, C., Nadji, M., Mian, M., Asotra, K., & Roos, B. A. (1999). Suppression of human prostate cancer cell growth by forced expression of connexin genes. Developmental Genetics, 24(1-2), 91-110.

Suppression of human prostate cancer cell growth by forced expression of connexin genes. / Mehta, Parmender P; Perez-Stable, Carlos; Nadji, Mehrdad; Mian, Mohsin; Asotra, Kamlesh; Roos, Bernard A.

In: Developmental Genetics, Vol. 24, No. 1-2, 16.03.1999, p. 91-110.

Research output: Contribution to journalArticle

Mehta, PP, Perez-Stable, C, Nadji, M, Mian, M, Asotra, K & Roos, BA 1999, 'Suppression of human prostate cancer cell growth by forced expression of connexin genes', Developmental Genetics, vol. 24, no. 1-2, pp. 91-110.
Mehta PP, Perez-Stable C, Nadji M, Mian M, Asotra K, Roos BA. Suppression of human prostate cancer cell growth by forced expression of connexin genes. Developmental Genetics. 1999 Mar 16;24(1-2):91-110.
Mehta, Parmender P ; Perez-Stable, Carlos ; Nadji, Mehrdad ; Mian, Mohsin ; Asotra, Kamlesh ; Roos, Bernard A. / Suppression of human prostate cancer cell growth by forced expression of connexin genes. In: Developmental Genetics. 1999 ; Vol. 24, No. 1-2. pp. 91-110.
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