MALIGNANT TO BENIGN TUMOR TRANSITION

总体目标是研究生长因子在结肠细胞中的作用。 利用本实验室建立的细胞库进行分化 一条父母系。这包括永久性的结肠癌细胞株。 致力于肠细胞，液体运输分化，HD3，HD4， 和U4H，一株肠道细胞前体细胞系U4，以及一株被阻断的 肠细胞成熟，HI1。所有这些细胞系都具有自分泌功能。 TGFb1负增长调控。第二组细胞系 包括致力于杯状细胞分化、HD6和HD8， 其不显示TGFb1的调制。第三组包含 HMBA、U9和HMBA耐药多层细胞系 Hp1，它利用TGFb1作为自分泌正向生长调节剂。它 将确定细胞是否致力于肠细胞分化- TION、HD3、HD4和U4H对TGFb1的生长抑制作用是通过 视网膜母细胞瘤基因产物的低磷酸化 发生在细胞周期以及对TGFb1耐药的细胞系 成熟到杯状细胞的HD6和HD8失去了TGFb1受体。 分化是否会干扰TGFAlpha自分泌生长刺激- 将通过比较配体和配体的表达来研究保守环 分化和未分化细胞中的受体。这一机制 分化结肠对碱性成纤维细胞生长因子的促有丝分裂反应丧失 肿瘤细胞中是否存在自分泌成纤维细胞生长因子途径 未分化的线条将被确定。三种可能的间接方式 TGFb1促进未分化结肠生长的机制 将对癌细胞进行检查。转染激活剂的效果观察 V-H-ras基因对杯状细胞和肠细胞分化的影响 细胞与细胞接触的必要性将通过 L-CAM葡萄胎蛋白对肠细胞和杯状细胞分化的影响。

The overall aim is study of the role of growth factors in colonocyte differentiation using the cell bank developed by this laboratory from one parental line. These include colon carcinoma cell lines permanently committed to enterocytic, fluid-transporting differentiation, HD3, HD4, and U4H, one enterocytic precursor cell line U4, and one line blocked in enterocytic maturation, HI1. All of these cell lines exhibit autocrine negative growth regulation by TGFbl. A second group of cell lines include those committed to goblet cell differentiation, HD6 and HD8, which display no modulation by TGFbl. The third group contains multilayered cell lines resistant to differentiation by HMBA, U9 and HP1, which utilize TGFbl as an autocrine positive growth regulator. It will be determined whether cells committed to enterocytic differentia- tion, HD3, HD4 and U4H, respond by growth inhibition to TGFbl through hypophosphorylation of the retinoblastoma gene product and where this occurs during the cell cycle and whether TGFbl-resistant cell lines maturing to goblet cells, HD6 and HD8, have lost TGFbl receptors. Whether differentiation interrupts a TGFalpha autocrine growth stimula- tory loop will be studied by comparing expression of both the ligand and receptor in differentiated and undifferentiated cells. The mechanism for loss of mitogenic response to basic FGF by differentiated colon carcinoma cells and whether autocrine FGF pathways exist in undifferentiated lines will be determined. Three possible indirect mechanisms for TGFbl-stimulation of growth of undifferentiated colon carcinoma lines will be examined. The effect of a transfected activated v-H-ras gene on goblet cell and enterocytic differentiation will be examined as will be the necessity of cell to cell contact through the L-CAM uvomorulin for enterocytic and goblet cell differentiation.