PARITY RESISTANCE TO MAMMARY CANCER--MOLECULAR ANALYSES

与怀孕或35岁以上首次足月怀孕的女性相比，早期首次足月怀孕的女性患乳腺癌的风险大大降低。产大鼠和小鼠对化学致癌物诱导的乳腺癌也几乎完全耐药。在过去的几年中，我们在了解大鼠和小鼠的奇偶性诱导的乳腺癌发生的生物学基础方面取得了相当大的进展。本提案的主要兴趣是通过扩大我们正在进行的使用大鼠实验模型的研究，在分子水平上研究奇偶诱导的耐火性的性质。我们的目标分为两部分。首先，我们希望研究易感（处女）或难治性（分娩或外源性激素治疗）乳腺对乳腺癌发生的差异基因表达。其次，我们希望对易感和难治性大鼠的两种不同暴露基因进行详细的表征和分析。我们认为，胎次和外源性激素治疗通过类似的机制诱导乳腺癌的难治性或保护。这些研究的最终目标是产生一种实验范例，可用于制定预防人类乳腺癌的战略，而不会对其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.