Accession Number : ADA304775

Title :   Multiple Genetic Alterations in Breast Cancer.

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

Corporate Author : M D ANDERSON CANCER CENTER HOUSTON TX

Personal Author(s) : Hung, Mien-Chie

PDF Url : ADA304775

Report Date : 14 SEP 1995

Pagination or Media Count : 53

Abstract : Overexpression of HER-2/neu and inactivation of estrogen receptor (ER) or the tumor suppressor gene, Rb, are known to be involved in the development of human breast cancer. Expression of HER-2/neu can be regulated by ER or Rb. In addition, expression of Heregulin, a recently cloned ligand for the HER-2/neu-encoded receptor has also been found in some breast cancer cells and may contribute to malignant transformation of breast cancer. The current proposal will focus on the role of HER-2/neu, Heregulin, ER, Rb, and their interrelationship in breast cancer. The technical objectives are: (1) Systematic studies on the expression of HER-2/nea, Heregulin, ER and Rb in breast tumor specimens and correlation of the expression with tumor stages and patient survival. (2) Potential paracrine and autocrine loops for HER-2/neu and Heregulin. (3) Effects of ER on malignant transformation phenotypes of HER-2/neu-overexpressing breast cancer cells. (4) Effects of Rb on malignant transformation phenotypes of HER-2/neu- overexpressing breast cancer cells. Expression of HER-2/neu, Heregulin, ER and Rb in the same breast tumor specimens will be examined by immunohistochemical staining, western, northern and in situ hybridization. The relationship between expression of these molecules, tumor grades, and patient's survival will be evaluated Using gene transfer technique, Heregulin, ER or Rb gene will be introduced into HER-2/neu-expressing breast cancer cells. The effect on their malignant transformations will be examined. This project may help to develop a more reliable molecular prognostic strategy and to understand how interactions among multiple genetic factors are involved in the development of breast cancer.

Descriptors :   *NEOPLASMS, *GENES, *SURVIVAL(PERSONNEL), *GENETICS, *MAMMARY GLANDS, *BREAST CANCER, HUMANS, MOLECULES, CELLS, CORRELATION, LIGANDS, CLONES, TRANSFER, PATIENTS, SENSE ORGANS, TRANSFORMATIONS, CANCER, INACTIVATION, SUPPRESSORS, HYBRIDIZATION, ESTROGENS.

Subject Categories : Medicine and Medical Research
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE