PARITY RESISTANCE TO MAMMARY CANCER--MOLECULAR ANALYSES

与已经怀孕或在35岁或35岁以上首次足月怀孕的妇女相比，妇女在早期发生第一次足月怀孕大大降低了患乳腺癌的风险。分娩的大鼠和小鼠对化学致癌诱导的乳腺癌也几乎完全耐受。在过去的几年里，我们在理解胎次诱导的大鼠和小鼠乳腺癌不耐药的生物学基础方面取得了相当大的进展。这项建议的主要兴趣是通过使用大鼠实验模型扩展我们正在进行的研究，在分子水平上研究产次诱导的不稳定的本质。我们的目标分为两部分。首先，我们希望研究对乳腺癌发生敏感(处女)或难治(经产时或外源性激素治疗)的乳腺之间的差异基因表达。其次，我们想要对易感和难治性大鼠中差异暴露的两个基因进行详细的表征和分析。我们认为，产次和外源性激素治疗通过类似的机制诱导对乳腺癌发生的抵抗或保护作用。这些研究的最终目标是产生一种实验范式，用于制定预防人类乳腺癌的策略，而不会对他们的健康和生活质量产生不利影响。

The occurrence of a first full term pregnancy at an early age in women profoundly decreases the risk of breast cancer compared to women have having been pregnant or women having a first full term pregnancy at age 35 or older. Parous rats and mice are also nearly completely resistant to mammary carcinogenesis induced by chemical carcinogenesis. During the last several years, we have made considerable progress in understanding the biological basis of parity-induced refractoriness to mammary carcinogenesis in rats and mice. The major interest of this proposal is to investigate the nature of parity-induced refractoriness at the molecular level by expanding our ongoing studies using the rat experimental model. Our objective is divided into two parts. First, we wish to investigate differential gene expression between mammary glands that are either susceptible (virgin) or refractory (parous or exogenous hormone treated) to mammary carcinogenesis. Second, we would like to undertake a detailed characterization and analysis of two genes differentially exposed in susceptible versus refractory rats. It is our belief that parity and exogenous hormonal treatment induce refractoriness to, or protection from mammary carcinogenesis by similar mechanisms. The ultimate goal of these studies is to generate an experimental paradigm that an be used to develop strategies for the prevention of human breast cancer without adverse effects on their health and quality of life.