Multiple Genetic Alterations in Breast Cancer.
Annual rept. 15 Aug 96-14 Aug 97
TEXAS UNIV AT HOUSTON
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Overexpression of HER-Zineu a member of the EGF receptor family 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-2neu can be regulated by ER or Rb. In addition, expression of other EGF receptor family genes EGF receptor, HER-3 and HER-4 and Heregulin, a ligand for the HER-3 and HER-4 encoded receptor has also been found in some breast cancer cells and may contribute to malignant transformation of breast cancer. The current progress report focuses on the role of the EGF receptor family genes, Heregulin, ER, Rb, and their interrelationship in breast cancer. The technical objectives are 1 Systematic studies on the expression of EGF receptor family genes, Heregulin, and ER in breast tumor specimens and correlation of the expression with tumor stages and patient survival 2 Potential paracrine and autocrine loops for EGF receptor family molecules and Heregulin 3 Effects of ER on malignant transformation phenotypes breast cancer cells and 4 Effects of Rb on malignant transformation phenotypes breast cancer cells. Expression of EGF receptor family genes, Heregulin, and ER in the same breast tumor specimens were examined by immunohistochemical staining, and western blotting. The relationship between expression of these molecules, tumor grades, and patients survival will be evaluated Using gene transfer technique, Heregulin, ER or Rb gene are being introduced into HER-2neu-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.
- Anatomy and Physiology
- Medicine and Medical Research