HOX genes and their role in the development of human cancers.

In this review, we summarize published findings on the involvement of HOX genes in oncogenesis. HOX genes are developmental genes--they code for proteins that function as critical master regulatory transcription factors during embryogenesis. Many reports have shown that the protein products of HOX genes also play key roles in the development of cancers. Based on our review of the literature, we found that the expression of HOX genes is not only up- or downregulated in most solid tumors but also that the expression of specific HOX genes in cancers tends to differ based on tissue type and tumor site. It was also observed that HOXC family gene expression is upregulated in most solid tumor types, including colon, lung, and prostate cancer. The two HOX genes that were reported to be most commonly altered in solid tumors were HOXA9 and HOXB13. HOXA were often reported to have altered expression in breast and ovarian cancers, HOXB genes in colon cancers, HOXC genes in prostate and lung cancers, and HOXD genes in colon and breast cancers. It was found that HOX genes are also regulated at the nuclear-cytoplasmic transport level in carcinomas. Tumors arising from tissue having similar embryonic origin (endodermal), including colon, prostate, and lung, showed relatively similar HOXA and HOXB family gene expression patterns compared to breast tumors arising from mammary tissue, which originates from the ectoderm. The differential expression of HOX genes in various solid tumors thus provides an opportunity to advance our understanding of cancer development and to develop new therapeutic agents.