Accession Number:

ADA422984

Title:

Mechanisms for C-Myc-Induced TGF - Prevented Mouse Mammary Tumors

Descriptive Note:

Annual rept. 15 Sep 2002-14 Sep 2003

Corporate Author:

GEORGETOWN UNIV WASHINGTON DC

Personal Author(s):

Report Date:

2003-10-01

Pagination or Media Count:

56.0

Abstract:

Many clinical studies have shown that apoptosis may be related to various pathological parameters of breast cancer, such as tumor size, histologic features, metastasis, and survival. Over 50 of human breast cancer biopsies show amplification or overexpression of c-myc, an oncogene that is known to play a crucial role in cell proliferation, apoptosis, and transformation. Female c-myc transgenic mice also develop mammary cancer that is characterized by a large number of apoptotic cells, thus serving as a good in vivo model for study on the role of c-Myc in both mammary carcinogenesis and apoptosis. On the other hand, TGFa, a growth factor also frequently overexpressed in human breast cancer, has been shown in MT-tgfaMMTV-c-myc double transgenic mice to enhance c-Myc-induced mouse mammary carcinogenesis, probably in part by blocking apoptosis. Our proposal set out to examine the c-Myc mechanisms of mediated apoptosis in our mouse mammary tumor model. In addition, we examined the survival-promototing effect of the TGFa-EGF receptor pathway in this model. We initially provided evidence for TGFa-EGF receptor emediated cell survival by a calciumcalmodulin mediated pathway regulating Akt. Subsequent studies have focused on the role of a recently discovered kinase, PNCK, and P55g, a p13 kinase subunit to mediate the EGF survival signal.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE