Accession Number:

ADB251995

Title:

Study the Pathogenic Role of ErbB-3, ErbB-4 and their Ligand Heregulin in Human Breast Cancer Cell

Descriptive Note:

Annual rept. 1 Jul 1998-30 Jun 1999

Corporate Author:

GEORGETOWN UNIV WASHINGTON DC

Personal Author(s):

Report Date:

1999-07-01

Pagination or Media Count:

82.0

Abstract:

Among the growth factor receptors, members of the class I receptor tyrosine kinase family ErbB is most frequently implicated in human breast cancers. To delineate the biological function of ErbB-4 receptors in breast cancer, we employed a hammerhead ribozyme strategy to achieve down-regulation of ErbB-4 receptors in various breast cancer cell lines. We observed that down-regulation of ErbB-4 in estrogen receptor positive ER cell lines MCF-7 and T47D resulted in a reduction of tumorigenicity both in vitro and in vivo. However, over time completely down-regulation of ErbB-4 in ER cell lines acquired the ability to up-regulate EGFR or ErbB-2 and progressed to a hormone-independent phenotype. These results mimics the clinical observation. Overexpression of EGFR and ErbB-2 is inversely correlated with ER. The expression of ErbB-4 was correlated with ER and PgR primary breast tumors by immunohistochemistry. These results suggested that ErbB-4 plays different roles in breast cancer progression.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE