Accession Number : ADA298709

Title :   The Genetic Analysis of the Role of NEU Differentiation Factor (Heregulin) in NEU-Induced Mammary Carcinomas in the Mouse.

Descriptive Note : Annual rept. 15 Jul 94-14 Jun 95,

Corporate Author : YALE UNIV NEW HAVEN CT SCHOOL OF MEDICINE

Personal Author(s) : Perkins, Archibald S.

PDF Url : ADA298709

Report Date : 13 JUL 1995

Pagination or Media Count : 8

Abstract : Utilization of the mouse to investigate the genetics of mammary carcinoma. Identification of cooperating oncogenes using MMTV-insertion mutagenesis. It is known that over-expression of normal neu in he breast can lead to an increase in mammary carcinomas in transgenic mice, but the tumors occur late, indicating that additional mutations are necessary. One can target these cooperating genes by insertional activation with MMTV. The isolation and characterization of activated genes by molecular cloning techniques may lead to the identification of novel oncogenes involved in murine mammary tumors, and perhaps analogous uman tumors as well. Although the ligand heregulin may not bind directly to the pi 85 neu receptor, they have been shown to activate neu kinase activity. Tumorigenesis via p185(neu) signaling pathways could occur via ligand dependent or ligand independent routes. The relative importance of these two route may be determined genetically. We Ian to test for cooperativity between neu and heregulin by creating transgenic mice that overexpress heregulin nd cross these to neu transgenics. A dramatic increase in tumor incidence in neu transgenic mice bearing a eregulin transgene would indicate an important role for this ligand in the process.

Descriptors :   *CARCINOGENS, *CANCER, *MAMMARY GLANDS, MOLECULES, ISOLATION, NEOPLASMS, MUTATIONS, IDENTIFICATION, LIGANDS, GENES, CLONES, MICE, UTILIZATION, GENETICS.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE