Ovarian Cancer pp 231-245 | Cite as

Homeobox Gene Expression in Ovarian Cancer

  • Susan M. Pando
  • Hugh S. Taylor
Part of the Cancer Treatment and Research book series (CTAR, volume 107)

Abstract

Homeobox genes control embryogenesis in both vertebrates and invertebrates. They are named after the highly conserved 180 bp sequence, the homeobox. There are two families of vertebrate homeobox genes. The first is the Hox genes and members of this family are clustered on the chromosome. These genes are classified according to sequence similarities as well as their position within the cluster[1]. The second group is divergent and members of this group are found throughout the genome. In invertebrates, the cluster is known as the homeotic complex, or HOM-C. The vertebrate family of homeobox genes is large; greater than 0.2% of the estimated 100,000 genes per genome may contain a homeobox with only a small number residing in the Hox cluster[2]. The HOM-C and Hox complexes contain homologous genes that are similar in both sequence and function in different organisms. These genes dictate body design in all embryos. The effects of vertebrate HOX genes can be ascertained from their expression pattern during mouse development and from the phenotype of mice with a targeted deletion, disruption or overexpression of a specific Hox gene [1].

Keywords

Ovarian Cancer Homeobox Gene Homeotic Gene Female Reproductive System Mesoblastic Nephroma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    McGinnis, W. and R. Krumlauf, Homeobox genes and axial patterning. Cell 1992; 68 (2): 283–302.CrossRefPubMedGoogle Scholar
  2. 2.
    Stein, S., et al., Checklist: vertebrate homeobox genes. Mech Dev 1996; 55 (1): 91108.CrossRefGoogle Scholar
  3. 3.
    Taylor, H.S., G.B. Vanden Heuvel, and P. Igarashi, A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes. Biol Reprod 1997; 57 (6): 1338–45.CrossRefPubMedGoogle Scholar
  4. 4.
    Lewis, E.B., A gene complex controlling segmentation in Drosophila. Nature, 1978; 276 (5688): 565–70.CrossRefPubMedGoogle Scholar
  5. 5.
    Sanchez-Herrero, E., et al., Genetic organization of Drosophila bithorax complex. Nature 1985; 313 (5998): 108–13.CrossRefPubMedGoogle Scholar
  6. 6.
    McGinnis, W., et al., A homologous protein-coding sequence in Drosophila homeotic genes and its conservation in other metazoans. Cell 1984; 37 (2): 403–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Scott, M.P. and A.J. Weiner, Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax, and fushi tarazu loci of Drosophila. Proc Natl Acad Sci U S A 1984; 81 (13): 4115–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Kissinger, C.R., et al., Crystal structure of an engrailed homeodomain-DNA complex at 2.8 A resolution: a framework for understanding homeodomain-DNA interactions. Cell 1990; 63 (3): 579–90.CrossRefPubMedGoogle Scholar
  9. 9.
    Qian, Y.Q., et al., The structure of the Antennapedia homeodomain determined by NMR spectroscopy in solution: comparison with prokaryotic repressors [published erratum appears in Cell 1990 May 4;61(3):548]. Cell 1989; 59 (3): 573–80.CrossRefPubMedGoogle Scholar
  10. 10.
    Wolberger, C., et al., Crystal structure of a MAT alpha 2 homeodomain-operator complex suggests a general model for homeodomain-DNA interactions. Cell 1991; 67 (3): 517–28.CrossRefPubMedGoogle Scholar
  11. 11.
    Manak, J.R. and M.P. Scott, A class act: conservation of homeodomain protein functions. Dev Suppl 1994: 61–77.Google Scholar
  12. 12.
    Duboule, D. and G. Morata, Colinearity and functional hierarchy among genes of the homeotic complexes. Trends Genet 1994; 10 (10): 358–64.CrossRefPubMedGoogle Scholar
  13. 13.
    Ruddle, F.H., et al., Evolution of chordate hox gene clusters. Ann N Y Acad Sci 1999; 870: 238–48.CrossRefPubMedGoogle Scholar
  14. 14.
    Scott, M.P., Vertebrate homeobox gene nomenclature [letter]. Cell 1992; 71 (4): 5513.CrossRefGoogle Scholar
  15. 15.
    Duboule, D. and P. Dolle, The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. EMBO J 1989; 8 (5): 1497–505.PubMedGoogle Scholar
  16. 16.
    Graham, A., N. Papalopulu, and R. Krumlauf, The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell 1989; 57 (3): 367–78.CrossRefPubMedGoogle Scholar
  17. 17.
    Lumsden, A. and R. Krumlauf, Patterning the vertebrate neuraxis. Science 1996; 274 (5290): 1109–15.CrossRefPubMedGoogle Scholar
  18. 18.
    lzpisua-Belmonte, J.C., et al., Murine genes related to the Drosophila AbdB homeotic genes are sequentially expressed during development of the posterior part of the body. EMBO J 1991; 10 (8): 2279–89.Google Scholar
  19. 19.
    Davis, A.P. and M.R. Capecchi, A mutational analysis of the 5’ HoxD genes: dissection of genetic interactions during limb development in the mouse. Development 1996; 122 (4): 1175–85.PubMedGoogle Scholar
  20. 20.
    Le Mouellic, H., Y. Lallemand, and P. Brulet, Homeosis in the mouse induced by a null mutation in the Hox-3.1 gene. Cell 1992; 69 (2): 251–64.CrossRefPubMedGoogle Scholar
  21. 21.
    Lufkin, T., et al., Homeotic transformation of the occipital bones of the skull by ectopic expression of a homeobox gene. Nature 1992; 359 (6398): 835–41.CrossRefPubMedGoogle Scholar
  22. 22.
    Muragaki, Y., et al., Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13 [see comments]. Science 1996; 272 (5261): 548–51.CrossRefPubMedGoogle Scholar
  23. 23.
    Dolle, P., et al., Disruption of the Hoxd-13 gene induces localized heterochrony leading to mice with neotenic limbs. Cell 1993; 75 (3): 431–41.CrossRefPubMedGoogle Scholar
  24. 24.
    Mortlock, D.P. and J.W. Innis, Mutation of HOXA13 in hand-foot-genital syndrome [see comments]. Nat Genet 1997; 15 (2): 179–80.CrossRefPubMedGoogle Scholar
  25. 25.
    Warot, X., et al., Gene dosage-dependent effects of the Hoxa-13 and Hoxd- 13 mutations on morphogenesis of the terminal parts of the digestive and urogenital tracts. Development 1997; 124 (23): 4781–91.PubMedGoogle Scholar
  26. 26.
    Devriendt, K., et al., Haploinsufficiency of the HOXA gene cluster, in a patient with hand-foot-genital syndrome, velopharyngeal insufficiency, and persistent patent Ductus botalli [letter]. Am J Hum Genet 1999; 65 (1): 249–51.CrossRefPubMedGoogle Scholar
  27. 27.
    Cunha, G.R., Stromal induction and specification of morphogenesis and cytodifferentiation of the epithelia of the Mullerian ducts and urogenital sinus during development of the uterus and vagina in mice. J Exp Zool 1976; 196 (3): 361–70.CrossRefPubMedGoogle Scholar
  28. 28.
    Taylor, H.S., et al., HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J Clin Invest 1998; 101 (7): 1379–84.PubMedGoogle Scholar
  29. 29.
    Taylor, H.S., et al., Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium. J Clin Endocrinol Metab 1999; 84 (3): 1129–35.CrossRefPubMedGoogle Scholar
  30. 30.
    Satokata, I., G. Benson, and R. Maas, Sexually dimorphic sterility phenotypes in Hoxa10-deficient mice. Nature 1995; 374 (6521): 460–3.CrossRefPubMedGoogle Scholar
  31. 31.
    Small, K.M. and S.S. Potter, Homeotic transformations and limb defects in Hox All mutant mice. Genes Dev 1993; 7 (12A): 2318–28.CrossRefPubMedGoogle Scholar
  32. 32.
    Hsieh-Li, H.M., et al., Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility. Development 1995; 121 (5): 1373–85.PubMedGoogle Scholar
  33. 33.
    Godwin, A.R. and M.R. Capecchi, Hoxc13 mutant mice lack external hair. Genes Dev 1998; 12 (1): 11–20.CrossRefPubMedGoogle Scholar
  34. 34.
    De Vita, G., et al., Expression of homeobox-containing genes in primary and metastatic colorectal cancer. Eur J Cancer 1993; 6: 887–93.CrossRefGoogle Scholar
  35. 35.
    Vider, B.Z., et al., Human colorectal carcinogenesis is associated with deregulation of homeobox gene expression. Biochem Biophys Res Commun 1997; 232 (3): 742–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Redline, R.W., et al., Expression of AbdB-type homeobox genes in human tumors. Lab Invest 1994; 71 (5): 663–70.PubMedGoogle Scholar
  37. 37.
    Cillo, C., et al., HOX gene expression in normal and neoplastic human kidney. Int J Cancer 1992; 51 (6): 892–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Anbazhagan, R. and V. Raman, Homeobox genes: molecular link between congenital anomalies and cancer. Eur J Cancer 1997; 33 (4): 635–7.CrossRefPubMedGoogle Scholar
  39. 39.
    Magli, M.C., C. Largman, and H.J. Lawrence, Effects of HOX homeobox genes in blood cell differentiation. J Cell Physiol 1997; 173 (2): 168–77.CrossRefPubMedGoogle Scholar
  40. 40.
    Deguchi, Y., J.F. Moroney, and J.H. Kehrl, Expression of the HOX-2.3 homeobox gene in human lymphocytes and lymphoid tissues. Blood 1991; 78 (2): 445–50.PubMedGoogle Scholar
  41. 41.
    Ziemin-van der Poel, S., et al., Identification of a gene, MLL, that spans the breakpoint in 11g23 translocations associated with human leukemias. Proc Natl Acad Sci USA 1991; 88 (23): 10735–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Yu, B.D., et al., Altered Hox expression and segmental identity in M11-mutant mice. Nature, 1995 378 (6556): 505–8.CrossRefPubMedGoogle Scholar
  43. 43.
    Borrow, J., et al., The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Nat Genet 1996; 12 (2): 159–67.CrossRefPubMedGoogle Scholar
  44. 44.
    Nakamura, T., et al., Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. Nat Genet 1996; 12 (2): 154–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Weis, K., et al., Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute promyelocytic leukemia cells. Cell 1994; 76 (2): 345–56.CrossRefPubMedGoogle Scholar
  46. 46.
    Yergeau, D.A., et al., Embryonic lethality and impairment of haematopoiesis in mice heterozygous for an AMLI-ETO fusion gene. Nat Genet 1997; 15 (3): 303–6.CrossRefPubMedGoogle Scholar
  47. 47.
    Celetti, A., et al., Characteristic patterns of HOX gene expression in different types of human leukemia. Int J Cancer 1993; 53 (2): 237–44.CrossRefPubMedGoogle Scholar
  48. 48.
    Greenlee, R.T., et al., Cancer statistics, 2000. CA Cancer J Clin; 2000; 50 (1): 7–33.CrossRefPubMedGoogle Scholar
  49. 49.
    Bast, R.C., Jr., et al., A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med 1983; 309 (15): 883–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Jacobs, I. and R.C. Bast, Jr., The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod 1989; 4 (1): 1–12.CrossRefPubMedGoogle Scholar
  51. 51.
    Mutch, D.G., Molecular characteristics of cancers: the way of the future?. Gynecol Oncol 2000; 77 (1): 8–10.CrossRefPubMedGoogle Scholar
  52. 52.
    Scott, M.P., J.W. Tamkun, and G.W.d. Hartzell, The structure and function of the homeodomain. Biochim Biophys Acta 1989; 989 (1): 25–48.PubMedGoogle Scholar
  53. 53.
    Holland, P.W. and B.L. Hogan, Expression of homeo box genes during mouse development: a review. Genes Dev 1988; 2 (7): 773–82.CrossRefPubMedGoogle Scholar
  54. 54.
    Redline, R.W., et al., Homeobox genes and congenital malformations. Lab Invest 1992; 66 (6): 659–70.PubMedGoogle Scholar
  55. 55.
    Beddington, R.S., A.W. Puschel, and P. Rashbass, Use of chimeras to study gene function in mesodermal tissues during gastrulation and early organogenesis. Ciba Found Symp 1992; 165: 61–74.PubMedGoogle Scholar
  56. 56.
    Bagot, C.N., P.J. Troy, and H.S. Taylor, Alteration of maternal HoxaI0 expression by in vivo gene transfection affects implantation. Gene Ther 2000; 7 (16): 1378–84.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Susan M. Pando
    • 1
  • Hugh S. Taylor
    • 1
  1. 1.Department of Obstetrics and GynecologyYale University School of MedicineNew HavenUSA

Personalised recommendations