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

口腔组织细胞从正常细胞转变为癌前细胞再转变为恶性细胞

• 批准号: 6201814
• 负责人: GEORGE E MILO
• 金额: $ 19.97万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6201814
• 关键词: antisense nucleic acid; athymic mouse; chemical carcinogen; gene expression; human tissue; molecular oncology; neoplasm /cancer genetics; neoplasm /cancer transplantation; neoplastic process; neoplastic transformation; oral mucosa; oral pharyngeal neoplasm; preneoplastic state; tobacco

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.

这项研究的长期目标是研究分子 人类正常或恶性转化所涉及的机制 烟草对口腔癌前细胞致瘤表型的影响 致癌物(TAC)。我们的初步数据表明，这一转换 直接涉及到一种新发现的肿瘤抑制因子的参与 吉恩，CATR1。这种基因似乎是独一无二的，并对 裸鼠癌前表型向致瘤表型转化的研究 老鼠。3041bpCATR1基因的1.3kbp反向序列已被克隆 制备并指定为反义cdna构建体。当插入到 RSVLTP启动子和真核表达载体及其转染 转化为非致癌的癌前细胞或致癌物质转化的人类细胞， 可以将这些细胞转化为肿瘤等致瘤表型。此外, 我们发现在人类口腔肿瘤中正常水平的转录产物 也被抑制了。我们的假设是CATR1消息级别是 口腔肿瘤的恶性程度与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的研究 该基因转录本表达水平降低的影响 细胞周期调控基因的调节，当烟草致癌物 用来将细胞转化或转化为恶性的。我们将继续追查此事 正常口腔时CATR1基因和细胞周期调控基因的变化 粘膜细胞转变为锚定非依赖生长阶段，并 一种恶性表型。美国海军2号将调查TAC的变化。 S.A.#.3将CATR1转录本的表达水平关联起来 肿瘤分级在人类表达中的建立和维持 正反义真核表达载体在口腔肿瘤治疗中的应用 表达的cdna构建。我们的目的是评估 CATR1和CATR1α表达水平与肿瘤恶性程度的关系 TAC转化和转化的细胞周期调控基因转录本 人类细胞与癌前病变和人类口腔癌 病人。