Disabled-2 Mediation of Retinoic Acid Cell Growth Arrest Signal in Breast Cancer
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 Ras/MAPK 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 and/or 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 activation/phosphorylation 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA410635
Entities
People
- Elizabeth R. Smith
Organizations
- Fox Chase Cancer Center