Retinoids regulate the formation and degradation of gap junctions in androgen-responsive human prostate cancer cells

Linda Kelsey, Parul Katoch, Kristen E. Johnson, Surinder Kumar Batra, Parmender P Mehta

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The retinoids, the natural or synthetic derivatives of Vitamin A (retinol), are essential for the normal development of prostate and have been shown to modulate prostate cancer progression in vivo as well as to modulate growth of several prostate cancer cell lines. 9-cis-retinoic acid and all-trans-retinoic acid are the two most important metabolites of retinol. Gap junctions, formed of proteins called connexins, are ensembles of intercellular channels that permit the exchange of small growth regulatory molecules between adjoining cells. Gap junctional communication is instrumental in the control of cell growth. We examined the effect of 9-cis-retinoic acid and all-trans retinoic acid on the formation and degradation of gap junctions as well as on junctional communication in an androgen-responsive prostate cancer cell line, LNCaP, which expressed retrovirally introduced connexin32, a connexin expressed by the luminal cells and well-differentiated cells of prostate tumors. Our results showed that 9-cis-retinoic acid and all-trans retinoic acid enhanced the assembly of connexin32 into gap junctions. Our results further showed that 9-cis-retinoic acid and all-trans-retinoic acid prevented androgen-regulated degradation of gap junctions, post-translationally, independent of androgen receptor mediated signaling. Finally, our findings showed that formation of gap junctions sensitized connexin32-expressing LNCaP cells to the growth modifying effects of 9-cis-retinoic acid, all-trans-retinoic acid and androgens. Thus, the effects of retinoids and androgens on growth and the formation and degradation of gap junctions and their function might be related to their ability to modulate prostate growth and cancer.

Original languageEnglish (US)
Article numbere32846
JournalPloS one
Volume7
Issue number4
DOIs
StatePublished - Apr 13 2012

Fingerprint

gap junctions
retinoids
Gap Junctions
retinoic acid
Retinoids
prostatic neoplasms
androgens
Tretinoin
Androgens
Prostatic Neoplasms
Cells
Degradation
Connexins
Vitamin A
degradation
Growth
Prostate
vitamin A
connexins
Communication

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Retinoids regulate the formation and degradation of gap junctions in androgen-responsive human prostate cancer cells. / Kelsey, Linda; Katoch, Parul; Johnson, Kristen E.; Batra, Surinder Kumar; Mehta, Parmender P.

In: PloS one, Vol. 7, No. 4, e32846, 13.04.2012.

Research output: Contribution to journalArticle

Kelsey, Linda ; Katoch, Parul ; Johnson, Kristen E. ; Batra, Surinder Kumar ; Mehta, Parmender P. / Retinoids regulate the formation and degradation of gap junctions in androgen-responsive human prostate cancer cells. In: PloS one. 2012 ; Vol. 7, No. 4.
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