MECHANISMS OF TGF BETA SIGNALING

Project: Research project

Project Details

Description

DESCRIPTION: (Applicant's abstract) TGF-beta may potentially be
successful in the treatment of epithelial cancers since it inhibits the
proliferation of responsive carcinoma cells and elicits differentiation-
like effects. However, many poorly differentiated or highly aggressive
carcinoma cells (i.e. colon, breast) have lost responsiveness to the
growth inhibitory effects of TGF-beta. Alterations in TGF-beta signaling
components likely represent major mechanisms underlying defects in TGF-
beta responsiveness, yet little is known regarding TGF-beta signaling
pathways, even in untransformed epithelial cells. During the previous
award period, the applicant cloned the rat homologue (termed RSmad1) of
MAD and has begun the functional analysis of this member of the Smad
superfamily of novel signaling components. In addition, phosphorylated
cytoplasmic regions of the TGF-beta receptors (CORT strategy) have been
used to clone additional novel TGF-beta signaling components. During the
next project period, guides will focus on determining the functional
role of the novel component(s) cloned by the CORT strategy in the
signaling of TGF-beta responses. Efforts with regard to the Smads will
focus on defining both the significance of the Smad1 signaling protein
in mediating specific TGF-beta responses, and the cross-talk between the
Smads, the Ras/MAPK and related pathways, and the novel signaling
pathways. The results obtained from this application will identify
targets for the development of therapeutics that will either mimic the
inhibitory effects of TGF-beta in epithelial cells or that will
eliminate the development of resistance to growth regulation by TGF-
beta.
StatusFinished
Effective start/end date4/7/953/31/03

Funding

  • National Cancer Institute: $278,891.00
  • National Cancer Institute

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.