GADD45 Family of Genes in Breast Cancer
Abstract
The primary objective of the proposed research was to investigate the role of the Gadd45 family of genes (Growth Arrest & DNA Damage) in breast carcinogenesis. A research plan was designed taking advantage of an established breast cancer prone mouse models (i.e. MMTV-ras and MMTV-myc mice) that were crossed with Gadd45alpha deficient mice. Generation of these mice allowed for the investigation of the role Gadd45alpha plays in breast cancer formation/progression. Tumorigenesis was accelerated in Ras/Gadd45alpha-/- mice compared to Ras/Gadd45alpha+/+ mice. The median tumor onset for Ras/Gadd45alpha-/- mice was 6 months of age, compared to 8 months for Ras/Gadd45alpha+/+. In addition, histological examination and grading of the tumors show the Ras/Gadd45alpha-/- specimen with higher histological grades than the Ras/Gadd45alpha+/+. Upon irradiation treatment, there was a significant increase in the tumor incidence, where 100% of the Ras/Gadd45alpha-/- mice developed tumors by 8 months of age compared to 12 months of age for the Ras/Gadd45alpha+/+ irradiated mice. The tumor growth rate and histological grades of the Ras/Gadd45alpha-/- irradiated tumors was significantly higher than that of the Ras/Gadd45alpha+/+. In MMTV-Myc mice, we have demonstrated that the loss of Gadd45alpha contributes to the deceleration of tumor formation. The mechanisms for acceleration/deceleration of breast tumorigenesis are an area of future investigation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA442347
Entities
People
- Dan A. Liebermann
Organizations
- Temple University