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) : Smith, Elizabeth R


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a410635.pdf


Report Date : Aug 2002


Pagination or Media Count : 26


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.


Descriptors :   *GROWTH(PHYSIOLOGY) , *BREAST CANCER , *RETINOIC ACIDS , ACTIVATION , EPITHELIUM , TISSUES(BIOLOGY) , ENZYMES , CELLS(BIOLOGY) , CULTURES(BIOLOGY) , MAMMARY GLANDS , PHOSPHORYLATION , VITAMIN A , METASTASIS , OVARIES


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE