Temporal Control of Transforming Growth Factor (TGF) - Betal Expression on Mammary Cell Multistep Transformation.

摘要

Transforming growth factor-beta (TGF-beta) is a pleiotropic growth factor, which plays a critical role in modulating cell growth, differentiation and plasticity. There is increasing evidence that after cells lose their sensitivity to TGF-beta-mediated growth inhibition, autocrine TGF-beta signaling may potentially promote tumor progression. In order to further understand the role of TGE-beta in mammary transformation, the MDA-MB-231 human metastatic breast cancer cell line was used to generate stable cell lines expressing a dominant negative TGE-beta type II receptor (dnT-beta-RII) . Expression of dnT- beta-RII was confirmed by affinity labeling cell surface receptors with 125I- TGF-beta-1 and immunoprecipitating the affinity labeled exogenous receptor via its HA tag. The dnT-beta-RII was determined to be functional in that it could associate with the type I TGf-beta receptor and prevent it from initiating signal transduction. Results to date indicate that the basal migratory potential of dnT-beta-RII expressing cells is impaired, and this impairment appears to be TGFp specific. Biochemical experiments are currently underway to identify the signal transducers perturbed by dnT-beta-RII expression which impair motility, and which may, in turn, be relevant to TGF-beta-mediated invasion and metastases.