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

本研究的长期目标是研究分子 涉及人类正常或恶性转化的机制 烟草相关的癌前口腔细胞致瘤表型 致癌物（TAC）。我们的初步数据表明这种转换 直接涉及新发现的抑癌基因的参与 基因，CATR1。该基因似乎是独特的并且负责 裸鼠癌前表型向致瘤表型的转化 老鼠。 3041 bp CATR1 基因的 1.3 kbp 反向序列已被 制备并指定为反义cDNA构建体。当插入 RSVLTP启动子和真核表达载体以及转染时 进入非致瘤性癌前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， 我们发现人类口腔肿瘤中转录物的正常水平 也都受到压制。我们的假设是 CATR1 消息级别是 与口腔肿瘤的恶性程度呈负相关。我们希望 研究正常口腔粘膜细胞和癌前表型 该基因转录表达水平降低的影响和 当烟草致癌物存在时，细胞周期调节基因的调节 用于将细胞转化或转变为恶性肿瘤。我们将追求这个 正常人口腔时总体CATR1基因和细胞周期调控基因 粘膜细胞转变为不依赖贴壁的生长阶段并 恶性表型。 S.A.#2 将调查 TAC 的变化。 S.A.#.3 将关联 CATR1 转录本的表达水平 与肿瘤分级在人类表达中的建立和维持 通过正义和反义真核细胞转染人类口腔肿瘤 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 TAC转化和转化中的细胞周期调控基因转录本 人类细胞和癌前病变以及人类口腔癌 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.