Accession Number:

ADA410635

Title:

Disabled-2 Mediation of Retinoic Acid Cell Growth Arrest Signal in Breast Cancer

Descriptive Note:

Final rept. 1 Aug 2001-31 Jul 2002

Corporate Author:

FOX CHASE CANCER CENTER PHILADELPHIA PA

Personal Author(s):

Report Date:

2002-08-01

Pagination or Media Count:

26.0

Abstract:

Loss of Disabled-2 Dab2 expression is frequently an early event in the tumorigenicity of breast and ovarian epithelial cancers. Retinoic acid RA treatment of F9 embryonic carcinoma cells induces Dab2 expression in both a time- and concentration-dependent manner suggesting Dab2 may be integral to the RA-mediated differentiation and development pathway. These studies undertook to investigate whether RA may mediate Dab2 expression in mammary epithelial cells, thereby inducing a negative regulator of the RasMAPK pathway. The ability of RA to induce Dab2 in breast carcinoma cell lines was assessed however, in no case did RA induce expression or alter the growth properties in these cell tines. Presumably an upstream regulator of the RA pathway andor Dab2 is deficient in these cells. Studies in F9 cells showed that Dab2 uncoupled MAPK activation from its downstream activation of c-Fos, and the affected step was the activationphosphorylation of the transcription factor, Elk-1. Thus, the loss of Dab2 in tumor cells may contribute to malignancy by removing a negative regulator of MAPK and c-Fos expression.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE