Impaired expression and posttranslational processing of connexin43 and downregulation of gap junctional communication in neoplastic human prostate cells.
BACKGROUND
Gap junctional communication (GJC) has been implicated in the control of cell proliferation. Numerous cancer cells show a decrease or loss of GJC compared to their normal counterparts. Lack of adequate information on the status of gap junctions during prostate neoplasia prompted us to examine this form of cancer, which comprises about 14% of male cancer deaths in America.


METHODS
Cultured normal human prostate epithelial cells and several different human prostate tumor lines were used in this study. GJC was assayed by dye transfer, whereas Western blot and immunofluorescence methods were used to examine connexin43 (Cx43) levels and the presence of gap junctions, respectively.


RESULTS
Normal human prostate cultures exhibited extensive cell-communication which was completely absent in all the examined tumor cells. This disrupted communication was associated with a decreased expression and an impaired posttranslational modification of Cx43 in these cells. Abundant immunostaining of gap junctional channels by a Cx43-antibody was observed in normal prostate cells but not in tumor cells.


CONCLUSIONS
Our data provide further support for the hypothesis that loss of junctional communication is a critical step in progression to human prostate neoplasia.
Hossain
M Z
MZ
Department of Molecular Medicine, Northwest Hospital, Seattle, Washington 98125, USA. mhossain@nwhsea.org
Jagdale
A B
AB
Ao
P
P
LeCiel
C
C
Huang
R P
RP
Boynton
A L
AL
D015153:Blotting, Western; D002450:Cell Communication / Q000235:genetics* / Q000502:physiology; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes / Q000737:chemistry; D017629:Gap Junctions / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D014407:Tumor Cells, Cultured