Transforming growth factor-beta inhibits rat intestinal cell growth by regulating cell cycle specific gene expression.
Transforming growth factor-beta 1 (TGF-beta 1) inhibits the growth of intestinal cells, but the mechanisms involved are unknown. Using a rat intestinal crypt cell line (IEC-6), we determined the site of action in the cell cycle that TGF-beta 1 acts to suppress proliferation. We also examined the effect of TGF-beta 1 on the expression of proliferation-associated "immediate early" genes (zif268, jun-B, c-myc) during the early G1 phase and the cdc2 gene during the transition from the G1 phase to the S phase of the cell cycle. Cell cycle progression was determined by incorporation of 3H-thymidine, and gene expression was analyzed by Northern blot analysis. We found that TGF-beta 1 acts to inhibit proliferation of rat intestinal crypt cells by blocking cell cycle progression at the middle G1 phase. The genes activated during G1 can be divided into TGF-beta 1 insensitive (zif268, jun-B, and c-myc) and TGF-beta 1 sensitive (the cdc2 gene). TGF-beta 1 suppresses the induction of the cdc2 gene during the G1/S transition without inhibiting the activation of immediate early genes during the early G1 phase.
Ko
T C
TC
Department of Surgery, University of Texas Medical Branch Galveston 77555-0533.
Beauchamp
R D
RD
Townsend
C M
CM
Thompson
E A
EA
Thompson
J C
JC
D000818:Animals; D015152:Blotting, Northern; D002453:Cell Cycle; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics*; D017781:Genes, Immediate-Early / Q000187:drug effects; D007399:Interphase; D007413:Intestinal Mucosa / Q000166:cytology*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000502:physiology*
D016212:Transforming Growth Factor beta