Abstract
Objective
Hox genes encode DNA transcription regulatory that contain a conserved 61 amino acid protein called the homeodomain. Although best known for their role in cellular differentiation during embryonic development, aberrant expression of these genes has been associated with hematologic and solid neoplasms. The purpose of this study was to determine the relative expression of HOXD10 in huamn endometrial adenocarcionmas.
Methods
mRNA was isolated from 7 normal endometrial specimens and 28 endometrial adenocarcinoma specimens. cDNA was synthesized using randon hexamer primers. The expression of HOXD10 relative to βtubulin (internal control) was assessed by densitometric comparison of co-amplified Phosphorus-32 (32P) labeled gene products separated by agarose gel electrophoesis. Direct sequencing of purified HOXD10 polymerase chain reaction product was also performed.
Results
The sequence of the purified HOXD10 product corresponds to the known DNA sequence reported in the National Institutes of Health Gene Bank. mRNA expression of HOXD10 relative to β-tubulin is significantly lower in endometrial carcinomas than in normal endometrium. Furthermore, the ratio of HOXD10 to β-tubulin expression varies inversely with the histologic grade of the tumor (P = .0009).
Conclusion
Cancer is a multistep proces involving aberrant expression of genes that regulate cell growth and differentiation. Human HOXD10 gene expression is altered in endometrial carcinoma and varies with the histologic grade of differentiation. This observation supports the theory that homeobox genes play a role in oncogenesis.
Similar content being viewed by others
References
McGinnis W, Levine MS, Hafen E, Kuroiwa A, Gehring WJ. A conserved DNA sequence in homoeotic genes of the Drosophila antennipedia and bithorax complexes. Nature 1984; 308: 428–33.
Gehring WJ. Homeoboxes in the study of development. Science 1987; 236: 1245–52.
Scott MP, Tamkum JW, Hartzell GW. The structure and function of the homeodomain. Biothem Biophys Acta (Rev Cancer) 1989; 989: 25–32.
Acampora D, D’Esposito M, Faiella A, et al. The human Hox gene family. Nucleic Acids Res 1989; 17: 10385–402.
Shashikant CS, Utset MF, Violette SM, et al. Homeobox genes in mouse development. Crit Rev Eurkaryotic Gene Expression 1991; 1: 207–45.
Shepherd JC, McGinnis W, Carrasco AE, De Robertis EM, Gehring WJ. Fly and frog homeo domains show homologies with yeast mating type regulatory type proteins. Nature 1984; 310: 70–7.
Duboule D, Dolle P. The structural and functional organization of the murine Hox gene family resembles that of Drosophila homeotic genes. EMBO J 1989; 8: 1497–505.
Akam M. HOX and HOM: Homologous gene clusters in insects and vertebrates. Cell 1989; 57: 347–49.
Scott MP. Vertebrate homeobox gene nomenclature. Cell 1992; 71: 551–3.
Boncinelli E, Acampora D, Pannese M, et al. Organization of human class I homeobox genes. Genome 1989; 31: 745–56.
Redline RW, Williams AJ, Patterson P, Collins T. Human HOX4E: A gene strongly expressed in the adult male and female urogenital tracts. Genomics 1992; 13: 425–30.
Cillo C, Barba G, Freschi G, Bucciarelli MC, Magli MC, Boncinelli E. Hox gene expression in normal and neoplastic human kidney. Int J Cancer 1992; 51: 892–7.
De Vita G, Barba P, Odartthenko N, et al. Expression of ho-meobox-containing genes in primary and metastatic colorectal cancer. Eur J Cancer 1993; 29A: 887–93.
Kongsuwan K, Webb E, Housiaux P, Adams JM. Expression of multiple homeobox genes within diverse mammalian haematopoietic lineages. EMBO J 1988; 7: 2131–39.
Blatt C, Aberdam D, Schwartz R, Sachs L. DNA rearrangement of a homeobox gene in myeloid leukaemic cells. EMBO J 1988; 7: 4283–90.
Kongsuwan K, Allen J, Adams JM. Expression of Hox–2.4 homeobox gene directed by proviral insertion in a myeloid leukemia. Nucleic Acids Res 1989; 17: 1881–92.
Redline RW, Hudock P, MacFee M, Patterson P. Expression of AbdB-type homeobox genes in human tumors. Lab Invest 1994; 71: 663–70.
Badley JE, Bishop GA, St John T, Frelinger JA. A simple rapid method for the purification of poly A RNA. Biotechniques 1988; 6: 114–6.
Sambrook J, Fritsch EF, Maniatas T, eds. Molecular cloning: A laboratory manual, 2nd ed. Cold Spring Harbor, New York: Cold Spnng Harbor Laboratory Press, 1989: E.5.
Lee MG, Lewis SA, Wilde CD, Cowam NJ. Evolutionary history of a multigene family: An expressed human beta-tubulin gene and three processed pseudogenes. Cell 1983; 33: 477–87.
Wang AM, Doyle MV, Mark DF. Quantitation of mRNA by the polymerase chain reaction. Proc Natl Acad Sci 1989; 86: 9717–21.
Kawasaki ES, Wang AM. Detection of gene expression. In: Erlich HA, ed. PCR technology: principles and applications of DNA amplification. New York: Stockton Press, 1989: 89–97.
Saiki RK, Gelfand DH, Stoffel S, et al. Primer directed enzymatic amplification of DNA with thermostable DNA polymerase. Science 1988; 239: 487–91.
Sambrook J, Fritsch EF, Maniatas T, eds. Molecular cloning: A laboratory manuel, 2nd ed. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press, 1989: 6.3–6.9.
Gehring WJ, Affolter M, Burglin T. Homeodomain proteins. Annu Rev Biothem 1994; 63: 487–536.
Deschamps J, Meijlink F. Mammahan homeobox genes in normal development and neoplasia. Crit Rev Oncogen 1992; 3: 117–73.
Aberdam D, Negreanu V, Sachs L, Blatt C. The oncogenic potential of an activated Hox 2.4 homeobox gene in mouse fibroblasts. Mol Cell Biol 1991; 11: 554–7.
Kamps MP, Muitc C, Sung X-H, Baltimore D. A new homeobox gene contributes to the DNA binding domain of the t(l; 19) translocation protein in pre-B ALL. Cell 1990; 60: 547–55.
Barba P, Magh MC, Tibeno C, Cillo C. Hox gene expression in human cancers. Adv Exp Med Biol 1993; 348: 45–57.
Shigemasa K, Hu C, West CM, et al. p16 overexpression: A potential early indicator of transformation in ovarian carcinoma. J Soc Gynecol Invest 1997; 4: 95–102.
Marshall CJ. Tumor suppressor genes. Cell 1991; 64: 313–26.
Author information
Authors and Affiliations
Additional information
Funded in part by the American Cancer Society Clinical Oncology Fellowship Award, grant 95–781.
Rights and permissions
About this article
Cite this article
Osborne, J., Hu, C., Hawley, C. et al. Expression of HOXDIO Gene in Normal Endometrium and Endometrial Adenocarcinoma. Reprod. Sci. 5, 277–280 (1998). https://doi.org/10.1177/107155769800500509
Published:
Issue Date:
DOI: https://doi.org/10.1177/107155769800500509