Ras is involved in gap junction closure in proliferating fibroblasts or preadipocytes but not in differentiated adipocytes.
A decrease in gap junctional, intercellular communication (GJIC) has been associated with cells neoplastically transformed by a variety of factors. To investigate the role of the Ras oncogene product in gap junction function, a panel of murine C3H10T1/2 (10T1/2) fibroblasts was constructed in which the levels of ras gene expression could be effectively up- or down-regulated. Intercellular communication was measured using a novel technique of in situ electroporation of adherent cells on a partly conductive slide. The introduction of increasing amounts of activated Ras(leu61) in mouse 10T1/2 fibroblasts proportionally reduced GJIC, while the downregulation of endogenous c-ras gene expression increased junctional permeability. These results indicate that Ras plays an important role in the junction closure pathway leading to the proliferation of normal cells. However, differentiation of c-Ras-deficient preadipocytes entirely abolished their initially extensive GJIC, indicating that junction closure in response to adipocytic differentiation is independent of Ras.
Brownell
H L
HL
Department of Microbiology, Queen's University, Kingston, Ontario, Canada.
Narsimhan
R P
RP
Corbley
M J
MJ
Mann
V M
VM
Whitfield
J F
JF
Raptis
L
L
D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D018274:Electroporation; D005347:Fibroblasts / Q000166:cytology*; D017629:Gap Junctions / Q000502:physiology*; D005786:Gene Expression Regulation; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D051379:Mice; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016372:RNA, Antisense
D016372:RNA, Antisense; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)