Relationship between HOX gene abnormality and investigation/metastasis of cancer cells in gynecologic malignancy

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In this study, we investigated expression profile of the HOX genes in ovarian and endometrial derived samples (normal ovarian and endometrial tissues and cancer cell lines) whether these cancer cells express HOX genes and examined effect of antisense introduction of the HOX genes whether overexpressed HOX genes involve manner of invasion/metastasis of the cancer cells. First, overexpression of the HOX genes in ovarian cancer cells (ES-2, SMOV-2, JHOC-6, SKOV-3, CAOV-3) and endometrial cancer cells (AN3CA, KLE, ISHIKAWA, HEC1A, HEC1B, RL-95) were analyzed by real-time PCR assay. It demonstrated that some of HOX genes are overexpressed in the cancer cells compared with that of normal counter parts. Especially, overexpression of HOXB13 is observed in both ovarian and endometrial cancers. Secondary, HOXB13 was used as a target gene for antisense introduction to the cancer cells. After construction of a vector for antisense introduction, it was introduced into the SKOV-3 and AN3CA cells by electroplating method. Conforming of the introduction of the antisense gene by cultivation and selection, inserted cells were transported to the matrigel chamber for matrigel assay to investigate that antisense DNA influences manner of invasion of the cancer cells. Culture and cell count of the cells on the membrane in the chamber revealed decreased number of cancer cells on the membrane in both ovarian and endometrial cancers, however in ovarian cancer, long term cultivation showed recovery of the number of the cancer cells. These results indicate important role of the HOX gene expression in both ovarian and endometrial cancers.