GADD45 Family of Genes in Breast Cancer
Abstract
The primary objective of the proposed research is to investigate the role of the Gadd45 family of genes (Growth Arrest & DNA Damage) (Gadd45alpha and Gadd45beta) in breast carcinogensis, which have been shown to play an important role in cell cycle control and response to anti-cancer agents. A research plan was designed taking advantage of established breast cancer prone mouse models (MMTV-v-Ras and MMTV-c-Myc) that were crossed with Gadd45alpha or Gadd45alpha/beta deficient mice. We have successfully generated mouse strains that are deficient for Gadd45alpha and breast cancer prone as a result of expression of oncogenic Myc (MMTV-c-Myc Gadd45alpha-/-) or activated Ras (MMTV-v-Ras Gadd45alpha-/-). Preliminary observations suggest breast tumorigenesis is accelerated in the MMTV-v-Ras Gadd45alpha-/- group when compared to the MMTV-v-Ras Gadd45alpha+/+ group. Tumors begin to appear in the MMTV-v-Ras Gadd45alpha-/- mice as early as 2 months of age, whereas the wild type mice do not seem to develop tumors until 5 months of age. Interestingly, Gadd45alpha+/- mice begin to develop tumors at 4 months of age, which suggests haplo-deficiency of Gadd45alpha is sufficient for acceleration of mammary tumor development. Another interesting observation is the increase in the number of tumors per mouse in the MMTV-v-Ras (Gadd45alpha-/- and MMTV-v-Ras Gadd45alpha+/- treatment groups compared to MMTV-v-Ras Gadd45alpha+/+ group. Results for MMTV-c-Myc mice are in the process of being collected and evaluated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA428239
Entities
People
- Dan A. Liebermann
Organizations
- Temple University