GENETIC ANALYSIS OF HUMAN MALIGNANCY

体细胞杂交研究清楚地证明了 抑制致瘤性现象。我们打算 确定参与肿瘤抑制的基因(S)和 描述它们的功能。最初，单个染色体 (Microcell)传输将用于识别特定的 携带肿瘤抑制基因的染色体(S)(S)。 将使用消减cdna杂交程序来克隆 这些基因。 我们还将研究肿瘤-- 抑癌基因(S)与癌基因。相关基因将是 插入到表达载体中，含有可诱导的MMTV- 正义和反义两种方向的ltr启动子。这个 改变正义和反义基因表达水平的效果 我们将对这些基因进行检测。 我们已经确定了一个候选的隐性癌基因 产物(p75肿瘤抗原)。我们打算克隆和刻画 编码p75的基因及其在肿瘤发生中的作用 HeLa细胞的行为。调节的反式作用基因 P75的表达也将被克隆和鉴定。这个 这种反式作用的调节基因可能是一种肿瘤- 将对抑制基因进行检测。

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.