TMIF--A NOVEL GROWTH INHIBITORY FACTOR/BREAST CARCINOMA

TMIF--一种新型生长抑制因子/乳腺癌

• 批准号: 2683583
• 负责人: E Premkumar Reddy
• 金额: $ 24.42万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2683583
• 关键词: antineoplastics; apoptosis; athymic mouse; breast neoplasms; cancer prevention; carcinoma; cell cycle; cell differentiation; chemoprevention; complementary DNA; female; growth inhibitors; high performance liquid chromatography; methylnitrosourea; neoplasm /cancer chemotherapy; nonhuman therapy evaluation; phosphorylation; protein purification; protein sequence; protein structure function; recombinant proteins; tissue /cell culture; tumor suppressor genes

Work in the recent past, especially with TGF-beta has suggested the existence of growth inhibitory actors which elicit a growth inhibitory effect on normal and neoplastic cells. It therefore appears that secretion of growth factors and growth inhibitors concomitant with selective spatial activation offers cells a mechanism to regulate their interactions with other cells and extracellular connective issues which may help explain many events in morphogenesis. In an attempt to determine if growth inhibitory factors exist which might specifically inhibit the growth of breast carcinoma cells, we undertook a study of screening a large number of human cell lines for secretary factors with such inhibitory activity. This resulted in the identification of one human B- lymphoid cell line which was found to secrete a growth inhibitory factor (TMIF-1) which appeared to inhibit the growth of several breast carcinoma cell lines without affecting the growth of several other cell types. This factor appears to be different from TGF-beta or any other known growth inhibitory factor. Preliminary evidence suggests that TMIF-1 is an 80 kda protein which is glycosylated. This research proposal is aimed at the biochemical characterization of this novel factor and molecular cloning of the gene that encodes for this factor. The aims of the proposal are 1. To purify TMIF-1 to homogeneity and obtain partial sequence of the protein factor; 2. To obtain cDNAs which encode for this factor; 3. To produce recombinant TMIF-1; 4. To study the mechanism of action of TMIF- 1; and 5. To test growth inhibitory properties of TMIF-1 in vivo using athymic nude mice implanted with mammary carcinomas. 6. To study the chemopreventive effects of TMIF-1 in female rats treated with methyl nitroso urea (MNU).

最近的研究，特别是关于tgf -的研究表明

项目成果

Inhibition of growth of estrogen receptor positive and estrogen receptor negative breast cancer cells in culture by AA-etherA, a stable 2-5A derivative.

• 发表时间: 1996-02
• 期刊: Oncogene
• 影响因子: 8
• 作者: K. Latham;S. Cosenza;R. Nl;E. Mordechai;Adelson Me;N. Kon;S. Horvath;R. Charubala;Mikhaĭlov Sn;W. Pfeiderer;Suhadolnik Rj