The mitogenic effects of transforming growth factors beta 1 and beta 2 in C3H/10T1/2 cells occur in the presence of enhanced gap junctional communication.
It has been proposed that the transfer of growth regulatory signals via gap junctions is important in the control of proliferation. In confluent 10T1/2 cells, growth control is enhanced by retinoids; this action is highly correlated with up-regulated gap junctional communication (GJC). Treatment of quiescent 10T1/2 cells with transforming growth factor (TGF) beta 1 and TGF-beta 2 resulted in elevated levels of proliferation together with increased expression of connexin43 protein and elevated GJC. Connexin43 was localized into plaques in regions of cell-cell contact; such plaques were found at high frequency in treated cells but only rarely in control cultures. These data illustrate that increased cell proliferation can occur in the presence of enhanced GJC, a result at variance with our previous results with retinoids. We suggest that either the proliferative stimulus of TGF-beta is sufficient to overwhelm any antiproliferative effect of GJC or that under conditions of TGF-beta stimulation, junctions convey net proliferative stimuli.
Gibson
D F
DF
Molecular Oncology Program, University of Hawaii, Honolulu 96813.
Hossain
M Z
MZ
Goldberg
G S
GS
Acevedo
P
P
Bertram
J S
JS
D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D018031:Connexin 43 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D018031:Connexin 43; D016212:Transforming Growth Factor beta