Autor: |
Li, Jonathan J., Li, Sara A., Llombart-Bosch, Antonio, Rajkumar, Lakshmanaswamy, Dang, Demi-Nhung, Hartnett, Mark D., Hirschberg, David L., Loh, Kenneth C., Guzman, Raphael C., Thordarson, Gudmundur, Nandi, Satyabrata |
Zdroj: |
Hormonal Carcinogenesis IV; 2005, p419-425, 7p |
Abstrakt: |
Pregnancy early in life reduces the risk of breast cancer (BC) in women and this effect is universal. This phenomenon is also observed in rodents. We have shown that a treatment with high pregnancy levels of 17β-estradiol (E2) for 7 to 21 days is effective in conferring protection against mammary carcinogenesis. We determined the difference in gene expression between hormone-protected rats and unprotected rats. Nine weeks old female Lewis rats were treated with 10 microgram (unprotected), or 200 microgram (protected) of E2 in silastic capsules for 3 weeks. Control rats received silastic capsules with no hormone. The rats were terminated 8 weeks after the removal hormone treatment. Mammary RNA was used for microarray analysis. Using Agilent Rat cDNA Microarrays, with 14,815 unique clones, we have analyzed genes from Rattus norvegicus and Rattus rattus which are annotated as "mRNA" or "gene EST" in GenBank. The genes involved in growth promotion like interleukin 18, kit oncogene, thyrotropin stimulating hormone receptor, cyclin dependent kinases etc. were down regulated in the protected group compared to the unprotected groups. In contrast, genes involved in growth inhibition like early growth response 1, insulin-like growth factor binding proteins and genes involve in apoptosis and DNA repair like T-cell death activated gene, CD47, histone acetyltransferase were up regulated in the protected animals compared to the unprotected. These findings define a pattern of gene expression that could serve to determine the efficacy of protective hormone treatments and help identify potential biomarkers for prevention of mammary cancers. [ABSTRACT FROM AUTHOR] |
Databáze: |
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