H0XC10, H0XC11, H0XD10, and H0XD11 mRNA levels dramatically decrease in the secretory phase at the time when progesterone levels rise rapidly. We had previously shown that H0XA10 and H0XA11 expression is rapidly induced in response to estrogen and progesterone in both stromal and Ishikawa cells. However, H0XC10, H0XC11, H0XD10, and H0XD11 expression was not altered by estrogen or progesterone in either primary stromal cells or Ishikawa endometrial adenocarcinoma cells. Hox genes typically cross-regulate each other’s activity and can act as transcriptional repressors of other homeobox genes. HOXC and HOXD genes may be regulated by HOXA genes or other transcriptional regulators.
Hox genes of any given paralogs are thought to function redundantly. Abd-B-related mammalian HOXC and HOXD genes may regulate identical or functionally equivalent downstream targets that may be involved in the regulation of cell proliferation during proliferative phase in the endometrium. The evidence showing overlapping function of Hox genes in mammals is particularly strong for members of any paralogous group. For most paralogous groups the encoded homeodomains are nearly identical, differing by zero to six amino acids, and Hox proteins have similar in vitro DNA target-binding specificities.