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During the last two decades, one group of homeobox containing genes, HOX genes family, has been studied not only in the context of embryogenesis but also in that of neoplasia. HOX genes consist of 39 different genes spread over 4 clusters, each designated HOX A, B, C and D on 4 different human chromosomes and are essential for control of cell fate in establishing a basic body pattern of mammalian embryo. The role of HOX genes is thought to provide certain molecular signals as a transcription factor necessary for cells movement. Therefore, it is possible that cancer cells re-activate these genes to move from a primary site to secondary sites in certain types of cancer. Recently, it is reported that abnormal expression of HOX genes has been found in a variety of malignancies and is involved in certain steps of carcinogenesis. However, little is known about the association between abnormal HOX functions and endometrial cancer, which is the most common malignancy of female genital tract. To investigate whether HOX genes contribute to invasive and metastatic characteristics of endometrial cancer cells, we initially created expression profile of HOX genes in endometrial derived samples (each of 12 normal samples from different individuals and endometrial cancer tissues from patients, and 6 different cancer cell lines). We found overexpression of HOXB13 mRNA in endometrial cancer cells and tissues from patient tumors using real-time RT-PCR assay. To elucidate whether overexpression of HOXB13 is responsible for invasion of endometrial cancer cells, we transfected antisense HOXB13/pcDNA3.1(+) plasmid vector into endometrial cancer AN3CA cells by electroporation and performed in vitro chemoinvasion assay using GFR MatrigelTM Invasion Chamber. We found that invasive ability of the antisense transfectant showed 90% reduction compared with that of parental cells and control transfectants. In addition, administration of 17beta-estradiol induced time- dependent and dose-dependent responses of the HOXB13 expression in endometrial cancer AN3CA cells. These results suggest that overexpression of HOXB13 in endometrial cancer may be involved in increasing the invasive ability of endometrial cancer cells under regulation by estrogen exposure.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]