CAF, A COACTIVATOR OF FOS, AND BREAST CANCER

Project: Research project

Project Details

Description

Recent studies in our laboratory have established that progression to
invasive human breast cancer is accompanied by the activation of tissue
factor (TF)-expressing myofibroblasts, a stromal response to carcinoma
cell-derived members of the TGF-beta family of growth factors.
Futhermore, TGF-beta1-dependent activation of TF gene transcription in
myofibroblast-like cells in vitro requires c-Fos-containing AP-1 DNA-
binding heterodimers and TF basal promoter-specific factor with
functional properties characteristic of a transcriptional coactivator.
This putative coactivator of Fos (CAF) appears distinct from CBP/p300
family of coactivators, but like CBP/p300, functionally interacts with
both c-Fos and the adenovirus E1A12s protein. Importantly, the ability
of CAF to mediate functional interactions with c-Fos is dependent upon
TGF-beta1 signaling. In this research, we will 1) map E1A domains which
specifically interact with CAF, 2) utilize this information to partially
characterize CAF and to isolate CAF protein and cDNA for sequence
analysis, 3) determine how the functional activity of CAF is modulated
by TGF-beta1 signaling, and 4) probe for the expression of CAF in breast
cancer myofibroblasts in vivo. These studies should illuminate a novel
downstream target of TGF-beta signaling in myofibroblasts and may
ultimately establish CAF as an essential mediator of carcinoma cell-
stromal interactions which contribute to breast cancer progression.
StatusNot started