Conjugated linoleic acid downregulates insulin-like growth factor-I receptor levels in HT-29 @entity1 XXXX cells.

@entity1 @entity1366 @entity10175 @entity5 @entity442 @entity584 @entity5100 @entity3962 @entity10412 @entity35 @entity2856 @entity694 @entity8569
Conjugated linoleic acid (CLA) has chemoprotective properties in a variety of experimental @entity5 models. We have previously observed that dietary CLA inhibits colon tumorigenesis induced by 1,2-dimethylhydrazine in @entity35 . In addition, our in vitro studies have shown that CLA inhibits DNA synthesis and induces apoptosis in HT-29 cells, the @entity1 @entity694 cell line. The insulin-like growth factor (IGF) system regulates the growth of HT-29 cells by an autocrine mechanism. The present study examined whether the growth inhibitory effect of CLA is related to changes in the IGF system in HT-29 cells. To determine whether CLA inhibits @entity5100 production, HT-29 cells were incubated in serum-free medium in the presence of various concentrations of CLA. CLA decreased protein levels of both mature and pro @entity5100 and @entity5100 transcripts. Whereas exogenous @entity442 and @entity5100 produced an increase in cell number, neither @entity442 nor @entity5100 counteracted the negative growth regulatory effect of CLA. Reverse transcriptase-polymerase chain reaction and Western blot analysis of total cell lysates revealed that CLA decreased @entity2856 ( @entity2856 ) transcript and protein levels in a dose-dependent manner. Immunoprecipitation/Western blot studies revealed that CLA inhibited @entity442 -induced phosphorylation of @entity2856 and @entity10175 , recruitment of the @entity8569 regulatory subunit of @entity10412 ( @entity10412 ) to @entity2856 , @entity2856 -associated @entity10412 activity, and phosphorylated @entity584 and @entity3962 levels. In conclusion, the inhibition of cell proliferation and induction of apoptosis by CLA in HT-29 cells may be mediated in part by its ability to decrease @entity5100 synthesis and to downregulate @entity2856 signaling and the @entity10412 / @entity584 and @entity1366 pathways.
