Impaired trafficking of connexins in androgen-independent human prostate cancer cell lines and its mitigation by α-catenin

Rajgopal Govindarajan, Sumin Zhao, Xiao Hong Song, Rong Jun Guo, Margaret Wheelock, Keith R Johnson, Parmender P Mehta

Research output: Contribution to journalArticle

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Abstract

Gap junctions, composed of connexins, provide a pathway of direct intercellular communication for the diffusion of small molecules between cells. Evidence suggests that connexins act as tumor suppressors. We showed previously that expression of connexin-43 and connexin-32 in an indolent prostate cancer cell line, LNCaP, resulted in gap junction formation and growth inhibition. To elucidate the role of connexins in the progression of prostate cancer from a hormone-dependent to -independent state, we introduced connexin-43 and connexin-32 into an invasive, androgen-independent cell line, PC-3. Expression of these proteins in PC-3 cells resulted in intracellular accumulation. Western blot analysis revealed a lack of Triton-insoluble, plaque-assembled connexins. In contrast to LNCaP cells, connexins could not be cell surface-biotinylated and did not reside in the cell surface derived endocytic vesicles, in PC-3 cells, suggesting impaired trafficking to the cell surface. Intracellular accumulation of connexins was observed in several androgen-independent prostate cancer cell lines. Transient expression of α-catenin facilitated the trafficking of both connexins to the cell surface and induced gap junction assembly. Our results suggest that impaired trafficking, and not the inability to form gap junctions, is the major cause of communication deficiency in human prostate cancer cell lines.

Original languageEnglish (US)
Pages (from-to)50087-50097
Number of pages11
JournalJournal of Biological Chemistry
Volume277
Issue number51
DOIs
StatePublished - Dec 20 2002

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Catenins
Connexins
Androgens
Prostatic Neoplasms
Cells
Cell Line
Gap Junctions
Connexin 43
Communication
Transport Vesicles
Tumors
Hormones
Western Blotting
Molecules
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Impaired trafficking of connexins in androgen-independent human prostate cancer cell lines and its mitigation by α-catenin. / Govindarajan, Rajgopal; Zhao, Sumin; Song, Xiao Hong; Guo, Rong Jun; Wheelock, Margaret; Johnson, Keith R; Mehta, Parmender P.

In: Journal of Biological Chemistry, Vol. 277, No. 51, 20.12.2002, p. 50087-50097.

Research output: Contribution to journalArticle

Govindarajan, Rajgopal ; Zhao, Sumin ; Song, Xiao Hong ; Guo, Rong Jun ; Wheelock, Margaret ; Johnson, Keith R ; Mehta, Parmender P. / Impaired trafficking of connexins in androgen-independent human prostate cancer cell lines and its mitigation by α-catenin. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 51. pp. 50087-50097.
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