HOST METABOLIC FACTORS THAT PREVENT PROGRESSION OF BREAST CANCER

防止乳腺癌进展的宿主代谢因素

• 批准号: 2464553
• 负责人: P OKUNIEFF
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 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/2464553
• 关键词: adenosine triphosphate; blood chemistry; breast neoplasms; caucasian American; chloride channels; clinical research; genetically modified animals; heterozygote; human subject; laboratory mouse; neoplasm /cancer genetics; neoplastic process; prostate neoplasms

The cystic fibrosis transmembrane regulator is abnormal in 4 or 5% of Caucasians. A single defective gene however causes no apparent harmful effects. Based on Dr. Abraham's discovery that the CFTR gene product acts as a transmembrane ATP transporter, we hypothesized that patients and animals that have CFTR heterozygosity will have a reduced propensity for the development of aggressive breast cancers. We have shown that heterozygous knockout mice at the CFTR locus grow breast cancers at a reduced rate and tumors in these animals have reduced aggressiveness compared to the wild type animals. Likewise, the homozygous knockouts had a severly reduced ability to grow breast cancers. It appears that this is due to the elevated ATP found in the blood of the heterozygous and homozygous knockout animals. We are therefore examining human Caucasian patients with breast cancer to determine if CFTR abnormalities are occurring at a reduced rate in these patients. We will also be measuring blood ATP levels in patients with breast cancer to determine if it is lower than expected. Finally, we are in the process of developing a similar protocol for screening patients with prostate cancers. A total of 420 are to be accrued with each disease.

囊性纤维化跨膜调节蛋白在4%或5%的 白种人 然而，一个单一的缺陷基因不会造成明显的有害影响， 方面的影响. 基于亚伯拉罕博士发现CFTR基因产物 作为跨膜ATP转运蛋白，我们假设患者和 具有CFTR杂合性的动物将具有降低的 侵袭性乳腺癌的发展。 我们已经证明 CFTR基因座的杂合敲除小鼠以100%的速度生长乳腺癌。 这些动物的发病率和肿瘤的侵袭性降低 与野生型动物相比。 同样，纯合子敲除 严重降低了乳腺癌的生长能力。 看来这是 由于在杂合子和 纯合子敲除动物。 因此，我们正在研究高加索人 乳腺癌患者，以确定CFTR异常是否 在这些患者中发生率降低。 我们还将测量 乳腺癌患者的血液ATP水平，以确定它是否是 低于预期 最后，我们正在开发一个 用于筛查前列腺癌患者的类似方案。 共 每种疾病应累计420。