Transforming growth factor-β1 (TGF-β1) 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-β1 acts to suppress proliferation. We also examined the effect of TGF-β1 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-β1 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-β1 insensitive (zif268, jun-B, and c-myc) and TGF-β1 sensitive (the cdc2 gene). TGF-β1 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.
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