Effect of Estrogen on Progression of Human Proliferative Breast Disease in Xenograft Model.
Annual rept. 1 Aug 94-31 Jul 95,
MICHIGAN CANCER FOUNDATION DETROIT
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We have utilized a xenograft model of early human breast cancer progression to identify genetic and cellular changes that occur during breast cancer development and to experimentally manipulate these changes to determine which alterations play a causal role in progression. Alterations in relevant markers, viz., ERPgR, p53, mdm-2, DNA methylation status and genomic instability were examined to determine if these correlate with progression. Methods utilized include injection of MCFl0AneoT and its derivatives into nudebeige mice and evaluation of lesionscultured cells by histology ER functionality by transient CAT assays p53 mutation by SSCP and sequencing genomic instability by development of drug resistance DNA methylation by Southern blotting, and gene expression by Northern and Western blotting. We show that ER expression occurs only in MCF 1 0AneoT and its derivatives. The ER is functionally active and responsive to E2. Activation of ER gene is not associated with hypomethylation in exon 1. Preliminary results indicate that estrogen may play a role in driving hyperplastic lesions to carcinoma. Genetic alterations in p53 are not responsible for neoplastic progression of MCF 1 OAneoT. The presence of a functionally active ER makes this model very useful to study the role of estrogen in neoplastic progression of human breast epithelial cells.
- Medicine and Medical Research
- Anatomy and Physiology