Conclusion

The data from the present investigation demonstrates that short-term treatment with 200 pg of E2, which results in high pregnancy levels of E2 in circulation, persistently alters the gene expression patterns. Although pregnancy levels of E2 with or without P conferred protection against mammary carcinogenesis, the mechanism of this protection is not clear. Our findings illustrate that there may be several different molecular pathways which may be altered in the protected animals. Recently, persistently altered expression of genes in the mammary glands ofparous rats was reported (24). In that report, certain genes involved in growth promotion were persistently down regulated in parous mammary glands; while and several of its transcriptional targets were up-regulated in parous mammary glands. Other investigators studying protection induced by E2+P treatment found persistent alterations in the expression of several known genes. Specifically, persistent changes in estrogen receptor (ERa), p53, and retinoblastoma binding protein (RbAp46) a gene implicated in the regulation of cell proliferation and differentiation following hormone treatment (25, 26) were identified.

Short-term treatment with high pregnancy levels of E2 resulted in persistent down-regulation of genes involved in growth promotion, cell cycle, anti-apoptosis, angiogenesis, and oncogenesis. On the other hand, the protective treatment persistently up-regulated genes involved in growth inhibition, apoptosis and DNA-repair. The data obtained could be helpful to understand the mechanisms involved in estrogen-induced protection and will also facilitate the identification of biomarkers associated with protection.

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