GENETIC ANALYSIS OF HUMAN MALIGNANCY

体细胞杂交研究已经清楚地表明， 抑制肿瘤发生的现象。 我们打算 鉴定参与肿瘤抑制的基因， 描述其功能。 最初，单个染色体 （微单元）传输将用于识别特定的 携带肿瘤抑制基因的染色体。 消减cDNA杂交程序将用于克隆 这些基因。 我们还将研究肿瘤之间的相互作用- 抑制基因和癌基因。 相关基因将是 插入表达载体，含有诱导型MMTV- LTR启动子，有义和反义方向。 的 改变正义和反义表达水平的效果 这些基因将被检测。 我们已经确定了一个候选的隐性致癌基因 产物（p75肿瘤抗原）。 我们打算克隆并描述 p75基因，探讨其在肿瘤发生中的作用 HeLa细胞的行为。 反式作用基因调节 p75的表达也将被克隆和表征。 的 这种反式调节基因是肿瘤的可能性 将检测抑制基因。

Somatic cell hybridization studies have clearly demonstrated the phenomenon of suppression of tumorigenicity. We intend to identify the gene(s) involved in tumor suppression and characterize their function. Initially, single chromosome (microcell) transfers will be used to identify specific chromosome(s) that carry the tumor-suppressor gene(s). Subtractive cDNA hybridization procedures will be used to clone these genes. We shall also investigate the interaction between tumor- suppressor gene(s) and oncogenes. The relevant genes will be inserted into expression vectors, containing an inducible MMTV- LTR promoter, in both sense and anti-sense orientations. The effect of varying the level of sense and anti-sense expression of these genes will be examined. We have already identified a candidate recessive oncogene product (p75 tumor antigen). We intend to clone and characterize the gene encoding p75 and investigate its role in tumorigenic behavior of HeLa cells. The trans-acting gene that regulates expression of p75 will also be cloned and characterized. The possibility that this trans-acting regulatory gene is a tumor- suppressor gene will be examined.