ALTERED POLYPEPTIDE EXPRESSION DURING MAMMARY CARCINOGENESIS

乳腺癌发生过程中多肽表达的改变

• 批准号: 3963583
• 负责人: P J WIRTH
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3963583
• 关键词: breast neoplasms; carcinogenesis; gene expression; molecular weight; oncoproteins; progesterone; tissue /cell culture

The project was initiated to identify and characterize tumor-associated protein changes during both human and experimental mammary carcinogenesis. Analysis of polypeptide changes during human mammary carcinogenesis revealed both qualitative and quantitative polypeptide differences. Six cytosolic polypeptides were expressed in all malignant tissues (eight individuals) but not in normal tissue, while one polypeptide (p52; pI 7.40/52 kDa) was not expressed during carcinogenesis. More numerous quantitative changes were also noted. These changes were localized mainly in the pI range 5.8-7.0 and molecular weight ranges of 22-40 kDa. Comparison of polypeptides in this region revealed a general up-regulation of polypeptide expression in malignant tissues as compared to those from normal mammary tissue. Included in this group of polypeptides is one polypeptide, p24 (pI 6.15/24 kDa), which was expressed in greatest concentrations in tissues exhibiting the highest estrogen receptor (ER) content. Expression of p24 was markedly reduced in normal tissue and in malignant tumors possessing low levels of progesterone receptor (PgR)/ER content. This polypeptide (p24) is distinct from any of the major known milk proteins and from the 24K protein of MCF-7 cells, a well-studied differentiation marker in human breast cancer.

该项目的发起是为了识别和表征与肿瘤相关的 蛋白质在人类和实验性乳腺癌发生过程中的变化。 人乳腺癌发生过程中多肽变化的分析 揭示了定性和定量多肽的差异。六 胞浆多肽在所有恶性组织中均有表达(8例 个体)，但在正常组织中不存在，而一种多肽(p52；p1 7.40/52 kDa)在癌变过程中不表达。更多 数量上的变化也被注意到。这些变化主要是局部性的 等电点为5.8-7.0，相对分子质量为22-40 kDa。 这一区域的多肽比较显示普遍上调 多肽在恶性肿瘤组织中的表达 正常的乳腺组织。这组多肽中包括一种 P24(等电点6.15/24 kDa)，表达水平最高 雌激素受体(ER)水平最高的组织中的浓度 内容。P24在正常组织和非小细胞肺癌组织中的表达显著降低。 孕激素受体(PGR)/ER水平低的恶性肿瘤 内容。这种多肽(P24)与已知的任何主要多肽都不同。 牛奶蛋白和来自MCF-7细胞的24K蛋白，研究得很好 乳腺癌中的分化标志物。