MECHANISM OF HORMONAL CONTROL OF MAMMARY CARCINOMA

24K雌激素调节蛋白是由我们的研究人员发现的。 在MCF-7人乳腺癌细胞实验室中， 制备抗体。 我们还准备了部分 测序了一个24K的cDNA，并发现了一个初步的同源性， 低分子量热休克蛋白。 24K蛋白是 发现集中在细胞的细胞质空泡中， 正常女性生殖组织的数量， 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，它的存在与雌激素相关 和孕激素受体，这表明它可能作为一种 分化和激素反应性的标志物。 我们现在提出三项研究来检查生物学和 乳腺肿瘤细胞24K的临床意义 (1)我们将 测定24K cDNA全序列， 为了确认与已知蛋白质的同源性， 热休克蛋白，并研究其可能的调控压力 以及类固醇激素。 (2)我们将使用24K，作为 雌激素调节蛋白，研究ER不一致的肿瘤 PgR状态 24K与受体不一致的肿瘤 还将审查地位。 ER中的特异性分子改变， PgR，或24K本身，这可能是预测的每一个这些 不一致性将在几个层面上进行测试， 将定义与临床结局不一致的每种类型。 (3)我们将确定24K是否具有有用的独立 通过测定乳腺肿瘤标本中的24K， 我们的肿瘤库的临床结果和许多已知的 预后因素（ER和PgR，淋巴结状态，DNA S期和 倍性，HER-2/neu癌基因扩增）可用于 相关性 我们还将测定24K， 用于多变量分析的新乳腺肿瘤标本中的因素 他们与复发和生存的关系， 临床可用。 这些研究将确定24K的功能特性， 区分乳腺癌预后良好和不良亚组的能力 ER和PgR不一致的肿瘤，以及其作为一种免疫调节剂的作用。 选择最佳治疗的独立预后因素 乳腺癌的治疗方法

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.