EXPRESSION AND HORMONE REGULATION OF WNT2,3,4,5A,7A,7B AND B-10 IN NORMAL HUMAN ENDOMETRIUM AND ENDOMETRIAL CARCINOMA

Wnt genes are transforming to mouse breast epithelium and are hormonal ly regulated in vivo. To assess their role in another endocrine-respon sive human cancer, the expression of seven Wnt genes (Wnt 2. 3, 4, 5a, 7a. 7b and 10b) in normal human endometrium and endometrial cells, an d endometrial carcinoma tissues and cell lines was investigated by rib onuclease protection analysis. Wnt2, 3, 4 and 5a mRNAs but not Wnt7a, 7b or 10b mRNAs were expressed in primary culture of normal endometria l epithelial (NEE) and stromal (NES) cells. In contrast, in four endom etrial carcinoma cell lines (RL95-2, HEC-1-A, AN3 CA and Ishikawa), Wn t2 and Wnt3 mRNAs were absent. Wnt4 was expressed in only one out of f our cell lines (RL95-2), and Wnt5a was much lower. Wnt7a and Wnt7b mRN As were expressed in three out of four cell lines (RL95-2, HEC-1-A and Ishikawa). Wnt10b mRNA was expressed in RL95-2 and AN3 CA. In fresh t issues, all Wnt genes ,part from Wnt10b were expressed in normal endom etrium and endometrial carcinoma. Similar to the cell lines, the fever of Wnt4 mRNA expression was significantly higher in the normal endome trium than endometrial carcinoma. Wnt2, 3 and 5a mRNAs were also lower in endometrial carcinoma compared with normal endometrium. There was no difference in the level of Wnt2, 3, 4 and 5a mRNA expression betwee n proliferative phase and secretory phase of the menstrual cycle, or b etween either menstrual phase and the first trimester of pregnancy. In vitro, progesterone and/or 17 beta-oestradiol had no effect on Wnt2, 3, 4, 5a and 7b mRNA expression in NES and all endometrial carcinoma c ell lines. The data indicate that all Wnt genes were expressed in vitr o, six out oi seven Wnt gene, (Wnt 2, 3, 4, 5a, 7a and 7b) were expres sed endogenously in the human endometrium, their mRNA expression was h ormonally independent and Wnt4 gene downregulation as well as down-reg ulation of Wnt 2, 3 and 5a may be associated with endometrial carcinom a.