CONVERSION OF CELLS IN ORAL TISSUE FROM NORMAL TO PREMALIGNANT TO MALIGNANT

这项研究的长期目标是研究分子 参与人类正常或恶性转化的机制 通过烟草相关的致癌性表型转化癌前口腔细胞 致癌物（TAC）。我们的初步数据表明， 直接涉及到一种新发现的肿瘤抑制因子的参与， 基因CATR1。这种基因似乎是独特的，负责 癌前表型转化为裸鼠致瘤表型 小鼠已克隆了3041 bp CATR 1基因的1.3 kbp反向序列， 制备并命名为反义cDNA构建体。当插入 RSVLTP启动子和真核表达载体， 转化为非致瘤性癌前病变或致癌物转化的人类细胞， 可以将这些细胞转化为肿瘤的致瘤表型。此外，本发明还提供了一种方法， 我们发现人类口腔肿瘤中转录本的正常水平 也被压制。我们的假设是CATR1信息水平是 与口腔肿瘤的恶性程度呈负相关。我们希望 在正常口腔粘膜细胞和癌前表型中， 该基因转录表达水平降低的影响， 调节细胞周期调控基因，当烟草致癌物 用于将细胞转化为恶性肿瘤。我们会追查下去 正常人口腔黏膜组织中CATR1基因和细胞周期调控基因的表达 粘膜细胞转化为锚定独立生长阶段， 恶性表型S.A. #2将研究TAC的变化。 S.A.编号3将CATR 1转录物的表达水平与 与肿瘤分级在人体内表达的建立和维持有关 通过转染正义和反义真核细胞的人口腔肿瘤的 表达cDNA构建体。我们的目的是评估 恶性肿瘤与CATR1表达水平之间的相关性， 细胞周期调控基因转录本在TAC转化和转化 人细胞和癌前病变及人口腔癌 患者

The long term objective of this research is to investigate the molecular mechanisms involved in the malignant conversion of either human normal or premalignant oral cells to tumorigenic phenotype by tobacco-associated carcinogens (TAC). Our preliminary data suggest that this conversion directly involves the participation of a newly discovered tumor suppressor gene, CATR1. This gene appears to be unique and responsible for the conversion of premalignant phenotypes to tumorigenic phenotypes in nude mice. A 1.3 kbp reverse sequence of the 3041 bp CATR1 gene has been prepared and designated as an antisense cDNA construct. When inserted into an RSVLTP promoter and eukaryotic expression vectors and when transfected into non-tumorigenic premalignant or carcinogen-transformed human cells, can convert these cells to tumorigenic phenotypes as tumors. In addition, we have found that the normal levels of transcripts in human oral tumors are also suppressed. Our hypothesis is that the CATR1 message level is inversely related to the degree of malignancy in oral tumors. We wish to investigate in normal oral mucosa cells and in premalignant phenotypes the effect of decreased levels of transcript expression of this gene and modulation of cell cycle regulatory genes, when tobacco carcinogens are used to transform or convert the cells to malignancy. We will pursue this overall CATR1 gene and cell cycle regulatory genes when normal human oral mucosa cells are converted to an anchorage independent growth stage and to a malignant phenotype. S.A. #2 will investigate the changes in TACs. S.A.#.3 will correlate the levels of expression of the CATR1 transcripts with tumor grade in human expression in the establishment and maintenance of human oral tumors by transfection of sense and antisense eukaryotic expression cDNA constructs. It is our intention to evaluate the correlation between malignancy and a levels of expression of CATR1 and cell cycle regulatory gene transcripts in TAC-transformed and converted human cells and premalignant lesions and oral carcinomas from human patients.