TMIF--A NOVEL GROWTH INHIBITORY FACTOR/BREAST CARCINOMA

最近的研究，特别是转化生长因子-β的研究表明， 存在可引起生长抑制的生长抑制因子 对正常细胞和肿瘤细胞的影响。因此，看起来 伴随着生长因子和生长抑制物的分泌 选择性空间激活为细胞提供了一种调节其功能的机制 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。在试图确定 如果存在生长抑制因子，可能会特异性地抑制 为了研究乳腺癌细胞的生长情况，我们进行了一项筛选 大量具有分泌因子的人类细胞系 抑制活性。这导致确认了一名人类B- 发现能分泌生长抑制因子的淋巴样细胞系 (TMIF-1)对几种乳腺癌的生长抑制作用 而不影响其他几种细胞类型的生长。这 因子似乎与转化生长因子-β或任何其他已知的生长因子不同 抑制因子。初步证据表明，TMIF-1是一个80KDA 糖基化的蛋白质。这项研究建议是针对 该新因子的生化特性及分子克隆 编码这一因子的基因。这项提议的目的是 1.纯化TMIF-1，获得部分序列。 蛋白质因子；2.获得编码该因子的cDNA；3. 产生重组TMIF-1；4.研究TMIF-1的作用机制 1、和5.体内检测TMIF-1的生长抑制特性 裸鼠移植乳腺癌。6.研究 TMIF-1对甲基染毒雌性大鼠的化学预防作用 亚硝基尿素(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).