EXPRESSION OF HOXD10 GENE IN NORMAL ENDOMETRIUM AND ENDOMETRIAL ADENOCARCINOMA

OBJECTIVE: Hox genes encode DNA transcription regulatory proteins that contain a conserved 61 amino acid protein called the homeodomain. Alt hough best known for their role in cellular differentiation during emb ryonic development, aberrant expression of these genes has been associ ated with hematologic and solid neoplasms. The purpose of this study w as to determine the relative expression of HOXD10 in human endometrial adenocarcinomas. METHODS: mRNA was isolated from 7 normal endometrial specimens and 28 endometrial adenocarcinoma specimens. cDNA was synth esized using random hexamer primers. The expression of HOXD10 relative to beta-tubulin (internal control) was assessed by densitometric comp arison of co-amplified Phosphorus-32 (P-32) labeled gene products sepa rated by agarose gel electrophoresis. Direct sequencing of purified HO XD10 polymerase chain reaction product was also performed. RESULTS: Th e sequence of the purified HOXD10 product corresponds to the known DNA sequence reported in the National Institutes of Health Gene Bank. mRN A expression of HOXD10 relative to reported in the National Institutes of Health Gene Bank. mRNA expression of HOXD10 relative to reported i n the National Institutes of Health Gene Bank. mRNA expression of HOXD 10 relative to beta-tubulin is significantly lower in endometrial carc inomas than in normal endometrium. Furthermore, the ratio of HOXD10 to beta-tubulin expression varies inversely with the histologic grade of the tumor (P = .009). CONCLUSION: Cancer is a multistep process invol ving the aberrant expression of genes that regulate cell growth and di fferentiation. Human HOXD10 gene expression is altered in endometrial carcinoma and varies with the histologic grade of differentiation. Thi s observation supports the theory that homebox genes play a role in on cogenesis. Copyright (C) 1998 by the Society for Gynecologic Investiga tion.