Effect of Estrogen on Progression of Human Proliferative Breast Cancer Disease in a Xenograft Model.
Abstract
We have utilized the T24-lla-ras transfected MCPi0A xenograft model of early human breast cancer progression to a) determine whether the observed epidemiologic link between estrogen and increased risk of breast cancer indeed reflect a direct growth promoting effect of estradiol (E2) On estrogen receptor positive (ER+) llBEC, and b) specify genetic and cellular changes that accompany (or characterize) the progression observed in successive transplant generations. The effects of E2 on neoplastic progression of llBEC were evaluated by examining the effects of E2 supplementation on progression ofMCFl0AneoT and its derivatives from the orthotopic site in ovariectomized female nude mice . Results indicate that E2 supplementation enhances conversion of lesions from grades 0/i (simple/moderate hyperplasia) to grades 3/4/5 (atypical hyperplasia/carcinoma in situ/invasive carcinoma), speeds the process of transformation, increases size of lesions, and promotes angiogenesis. Our data also indicate that alterations in expression of Bcl-2, cyclin Dl, c-erbB-2 and pS2 are valid correlative markers for progression. Our data show the presence of at least two pathways of wild-type p53 flinctional inactivation in MCFl0AT xenografts: one via a flinctionally inactive conformation and other via association of native wild type p53 with mdm-2.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA338019
Entities
People
- P. V. Shekhar
Organizations
- NATO