ESTROGEN-DEPENDENT TUMOR GROWTH AND ANGIOGENESIS

雌激素化合物在乳腺癌中起着关键作用， 子宫，在某些情况下还有肝脏，但它们的分子位置 行动不被理解。一种独特的雌激素调节肿瘤模型 生长和血管生成有坚实的遗传基础，是雌激素- 诱导Fischer 344品系大鼠垂体瘤生长。这些 肿瘤的生长和血管生成均表现为对 己烯雌酚或雌二醇。我们之前已经证明了 这些雌激素诱导的肿瘤的遗传基础是少数(2-4)个 基因。最近，我们对雌激素依赖性肿瘤进行了基因分离。 生长和血管生成。这两个性状都取决于多个基因。 但新生血管需要基因交互作用(上位性) 而总体增长是一个简单的加性性状。这些 这些发现迫使我们试图绘制和克隆负责基因的图谱 雌激素依赖的F344大鼠垂体瘤的形成。 具体地说，在我们的第一个目标中，我们将确定肿瘤的联系 利用数量性状区间分析分子标记的形成位点 映射。为了绘制肿瘤生长图，我们将使用肿瘤质量和 DNA含量。为了绘制肿瘤血管生成的基因图谱，我们将利用这些特征 出血外观和血管生成的生化指标， 如血红蛋白含量和CD31水平。在我们的第二个目标中，我们将 培育含有肿瘤耐药基因的重组近交系大鼠 来自棕色挪威株的遗传背景来自费舍尔 紧张。这些新品系将被用来精细定位这些基因，从而导致 我们的第三个主要目标；定义肿瘤生长和血管生成基因 分子水平。我们将在订单上以高分辨率绘制基因图谱 1厘米摩根。

Estrogenic compounds play a critical role in cancer of the breast, uterus, and in some cases the liver, but the molecular sites of their action are not understood. A unique model of estrogen regulation of tumor growth and angiogenesis that has a firm genetic basis is the estrogen- induced growth of pituitary tumors in the Fischer 344 rat strain. These tumors display both increased growth and angiogenesis in response to either diethylstilbestrol or estradiol. We previously showed that the genetic basis for these estrogen-induced tumors is a small (2-4) number of genes. Recently, we genetically separated estrogen-dependent tumor growth and angiogenesis. Both traits are dependent upon multiple genes but neovascularization requires gene interaction (epistasis) for expression whereas overall growth is a simple additive trait. These findings compel us to attempt to map and clone the genes responsible for estrogen-dependent pituitary tumor formation in the F344 rat. Specifically, in our first aim, we will determine the linkage of tumor formation loci to molecular markers by quantitative trait interval mapping. To map tumor growth, we will use the traits of tumor mass and DNA content. To map genes for tumor angiogenesis, we will use the traits of hemorrhagic appearance and biochemical indicators of angiogenesis, such as hemoglobin content and CD31 levels. In our second aim, we will breed recombinant inbred lines of rats that contain tumor resistant genes from the Brown Norway strain in a genetic background from the Fischer strain. These new lines will be used to fine map these genes, leading to our third major aim; defining tumor growth and angiogenesis genes at the molecular level. We will map the genes with high resolution on the order of 1 centiMorgan.