TMIF--A NOVEL GROWTH INHIBITORY FACTOR/BREAST CARCINOMA

最近的研究，特别是TGF-β的研究表明， 存在引起生长抑制的生长抑制因子 对正常和肿瘤细胞的影响。因此看来， 生长因子和生长抑制剂的分泌伴随着 选择性的空间激活为细胞提供了一种调节其 与其他细胞的相互作用和细胞外连接问题， 可能有助于解释形态发生中的许多事件。以试图确定 如果存在可能特异性抑制 乳腺癌细胞的生长，我们进行了一项研究， 大量人类细胞系分泌具有这种 抑制活性这导致了一个人的B- 发现分泌生长抑制因子的淋巴样细胞系 （TMIF-1），其似乎抑制几种乳腺癌的生长， 细胞系，而不影响其他几种细胞类型的生长。这 这一因子似乎不同于TGF-β或任何其他已知的生长因子， 抑制因子初步证据表明，TMIF-1是一个80 kda的， 糖基化的蛋白质。这项研究计划旨在 这种新因子的生化特性和分子克隆 编码这个因子的基因。该提案的目的是 1.为了将TMIF-1纯化至均一并获得TMIF-1的部分序列， 蛋白质因子; 2.获得编码该因子的cDNA; 3.到 产生重组TMIF-1; 4.研究TMIF的作用机制， 1;和5.为了测试TMIF-1在体内的生长抑制特性，使用 植入乳腺癌的无胸腺裸鼠。6.研究 TMIF-1在甲基化处理的雌性大鼠中的化学预防作用 亚硝基脲（MNU）。

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).