MECHANISM OF HORMONAL CONTROL OF MAMMARY CARCINOMA

24K雌激素调节蛋白是由我们的 实验室用MCF-7人乳腺癌细胞和单抗 制备抗体。我们还准备了部分 对一个24K的cDNA进行了测序，并发现与 低分子量热休克蛋白。24K蛋白是 被发现集中在一个细胞的细胞质空泡中 正常女性生殖组织的数量以及在一些 子宫内膜肿瘤，以及许多但不是所有的乳腺肿瘤。 在乳腺肿瘤中，它的存在与雌激素有关。 和孕激素受体，这表明它可能作为一种 分化和激素反应的标记物。 我们现在提出三项研究，以检验生物和 乳腺肿瘤细胞中24K的表达及其临床意义(1)我们会 确定全长24K的核苷酸序列，搜索 用于确认与已知蛋白质的同源性，包括 热休克蛋白，并检测其在应激中的可能调节 因素以及类固醇激素的作用。(2)我们将使用24K，作为 雌激素调节蛋白，用于研究ER不一致的肿瘤 和PGR状态。24K与受体不一致的肿瘤 状态也将被检查。内质网中的特异性分子改变， Pgr，或24K本身，这可能由其中的每一个预测 不和谐将在几个层面上进行测试，以及它们之间的关系 每种类型与临床结果的不一致性将被定义。 (3)我们将确定24K是否具有有用的独立性 乳腺癌标本中24K检测的预后价值 我们的肿瘤库的临床结果和许多人都知道 预后因素(ER和PgR、淋巴结状态、DNA S分期和 倍性，HER-2/neu癌基因扩增)可用于 相关性。我们还将同时测定24K 用于多变量分析的新的乳腺肿瘤标本中的因素 作为随访，它们与复发和生存的关系 临床应用变得可用。 这些研究将确定24K的功能同一性，其 区分乳房预后良好和不良亚组的能力 ER和PGR不协调的肿瘤及其作为一种 选择最佳治疗方案的独立预后因素 针对个别乳腺癌患者的策略。

The 24K estrogen-regulated protein was discovered by our laboratory in MCF-7 human breast cancer cells, and a monoclonal antibody was prepared. We have also prepared and partially sequenced a 24K cDNA, and found a tentative homology with the low molecular weight heat shock proteins. The 24K protein is found to be concentrated in cytoplasmic vacuoles in the cells of a number of normal female reproductive tissues and in some endometrial tumors, and also in many but not all breast tumors. In breast tumors, its presence is correlated with that of estrogen and progesterone receptors, suggesting its possible utility as a marker of differentiation and hormone responsiveness. We now propose three studies to examine the biological and clinical significance of 24K in breast tumor cells. (1) We will determine the complete 24K cDNA nucleotide sequence, search for confirmation of homology with known proteins including the heat shock proteins, and examine its possible regulation by stress factors as well as by steroid hormones. (2) We will use 24K, as an estrogen-regulated protein, to study tumors with discordant ER and PgR status. Tumors in which 24K is discordant with receptor status will also be examined. Specific molecular alteration in ER, PgR, or 24K itself which might be predicted by each of these discordances will be tested at several levels, and the relationship of each type of discordance with clinical outcome will be defined. (3) We will determine whether 24K has useful independent prognostic value, by assaying 24K in breast tumor specimens from our Tumor Bank for which clinical outcome and many known prognostic factors (ER and PgR, nodal status, DNA S-phase and ploidy, HER-2/neu oncogene amplification) are available for correlation. We will also assay 24K in parallel with the other factors in new breast tumor specimens, for multivariate analysis of their association with recurrence and survival as follow-up clinical becomes available. These studies will determine the functional identity of 24K, its ability to discriminate good and bad prognosis subgroups in breast tumors with discordant ER and PgR, and its role as an independent prognostic factor for selecting optimum treatment strategies for individual breast cancer patients.