PARITY RESISTANCE TO MAMMARY CANCER--MOLECULAR ANALYSES

与已经怀孕的女性或35岁或以上首次足月妊娠的女性相比，女性早期首次足月妊娠的发生大大降低了乳腺癌的风险。经产大鼠和小鼠也几乎完全抵抗化学致癌作用诱导的乳腺癌。在过去的几年中，我们已经取得了相当大的进展，在了解胎次诱导的难治性乳腺癌发生在大鼠和小鼠的生物学基础。这个建议的主要兴趣是通过扩大我们正在进行的研究，使用大鼠实验模型，在分子水平上调查奇偶校验引起的不应性的性质。我们的目标分为两部分。首先，我们希望研究乳腺癌易感（处女）或难治性（经产或外源性激素治疗）乳腺之间的差异基因表达。其次，我们想进行一个详细的表征和分析的两个基因差异暴露在易感与难治大鼠。我们认为，产次和外源性激素治疗通过类似的机制诱导乳腺癌发生的难治性或保护作用。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.