Development of gene diagnosis and therapy for endometrial cancers.

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Introduction of a single chromosome 1 derived from normal fibroblasts into HHUA endometrial carcinoma resulted in suppression of tumorigenicity. This tumorigenic suppression was accompanied by remarkable morphological changes. The microcell hybrids were characterized by intracellular actin formation and an excessive accumulation of actin and vinculin. The latter was a result of increased stabilization of the proteins.Introduction of a human chromosome 1 or 18 by microcell-mediated chromosome transfer has been shown to induce senescence of human endometrial cancer cells. This suggested that two different normal chromosomes induce senescence in the some human endometrial carcinoma cell line, being compatible with the idea that multiple pathways to senescence are inactivated in this cell line.Allelic losses on chromosome 17p and 18q have been associated with human endometrial carcinomas. In order to confirm involveament of the p53 gene in endometrial carcinogenesis, we searched for nucleotide sequence change in this gene in 42 carcinomas. Two cancers with LOH on 17p contained a mutant p53 gene in the allele that was retained. One speciwen with a p53 gene mutation contained a 17q deletion but was uninformative for LOH on 17p. P53 gene mutation was also noted in the remaining cancer, though the 17p deletion was not detected. Consideration of clinical stages in these 4 cancers suggested that with p53 gene mutations were involved in endometrial cancer progression.We analyzed LOH at 3 loci on 18q and DCC gene expression to define the gene of importance on 18q in endometrial cancers. The tumors possibly involved the region within or near the 18q 21.3 band where the DCC gene was localized. Moreover, the incidence of altered DCCmRNA expression was high (14/28,50%). The data suggested that the targer for LOH on 18q seen in endometrial cancers was the DCC gene, and that inactivation of this gene might be critical for the development of most endometrial cancers.