Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1995 Sep;147(3):586–592.

Cdx-2 homeodomain protein expression in human and rat colorectal adenoma and carcinoma.

H C Ee 1, T Erler 1, P S Bhathal 1, G P Young 1, R J James 1
PMCID: PMC1870974  PMID: 7677172

Abstract

Cancers share many similarities in growth patterns, cellular morphology, and oncofetal antigen expression with embryonic tissue. To better understand the mechanisms underlying malignant transformation and its relationship to developmental processes, we studied the expression of Cdx-2, an intestinal epithelium-specific homeodomain protein, in colorectal adenoma and carcinoma. By immunohistochemistry with a polyclonal Cdx-2 antibody we have shown that Cdx-2 expression is markedly reduced in the later stages of human colorectal carcinogenesis, namely, high grade dysplasia and invasive carcinoma. The same findings occur in 1,2-dimethylhydrazine-induced rat colorectal tumors, confirming the parallels between the rat model and the human disease. As homeodomain proteins play major roles in directing the regionalization of body parts and in organogenesis and cellular phenotypic specification, a reduction of Cdx-2 expression in the late stages of colorectal carcinogenesis may reflect a concomitant deviation of the neoplastic tissue from the normal intestinal epithelial phenotype.

Full text

PDF
586

Images in this article

588Figure 1
on p.588
589Figure 2
on p.589

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahnen D. J. Are animal models of colon cancer relevant to human disease. Dig Dis Sci. 1985 Dec;30(12 Suppl):103S–106S. doi: 10.1007/BF01296987. [DOI] [PubMed] [Google Scholar]
  2. Cillo C., Barba P., Freschi G., Bucciarelli G., Magli M. C., Boncinelli E. HOX gene expression in normal and neoplastic human kidney. Int J Cancer. 1992 Jul 30;51(6):892–897. doi: 10.1002/ijc.2910510610. [DOI] [PubMed] [Google Scholar]
  3. De Vita G., Barba P., Odartchenko N., Givel J. C., Freschi G., Bucciarelli G., Magli M. C., Boncinelli E., Cillo C. Expression of homeobox-containing genes in primary and metastatic colorectal cancer. Eur J Cancer. 1993;29A(6):887–893. doi: 10.1016/s0959-8049(05)80432-0. [DOI] [PubMed] [Google Scholar]
  4. Dedera D. A., Waller E. K., LeBrun D. P., Sen-Majumdar A., Stevens M. E., Barsh G. S., Cleary M. L. Chimeric homeobox gene E2A-PBX1 induces proliferation, apoptosis, and malignant lymphomas in transgenic mice. Cell. 1993 Sep 10;74(5):833–843. doi: 10.1016/0092-8674(93)90463-z. [DOI] [PubMed] [Google Scholar]
  5. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  6. Jacoby R. F., Llor X., Teng B. B., Davidson N. O., Brasitus T. A. Mutations in the K-ras oncogene induced by 1,2-dimethylhydrazine in preneoplastic and neoplastic rat colonic mucosa. J Clin Invest. 1991 Feb;87(2):624–630. doi: 10.1172/JCI115039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. James R., Erler T., Kazenwadel J. Structure of the murine homeobox gene cdx-2. Expression in embryonic and adult intestinal epithelium. J Biol Chem. 1994 May 27;269(21):15229–15237. [PubMed] [Google Scholar]
  8. James R., Kazenwadel J. Homeobox gene expression in the intestinal epithelium of adult mice. J Biol Chem. 1991 Feb 15;266(5):3246–3251. [PubMed] [Google Scholar]
  9. Kamps M. P., Baltimore D. E2A-Pbx1, the t(1;19) translocation protein of human pre-B-cell acute lymphocytic leukemia, causes acute myeloid leukemia in mice. Mol Cell Biol. 1993 Jan;13(1):351–357. doi: 10.1128/mcb.13.1.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Li S., Crenshaw E. B., 3rd, Rawson E. J., Simmons D. M., Swanson L. W., Rosenfeld M. G. Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. Nature. 1990 Oct 11;347(6293):528–533. doi: 10.1038/347528a0. [DOI] [PubMed] [Google Scholar]
  11. Magdelénat H. Tumour markers in oncology: past, present and future. J Immunol Methods. 1992 Jun 24;150(1-2):133–143. doi: 10.1016/0022-1759(92)90072-2. [DOI] [PubMed] [Google Scholar]
  12. McGinnis W., Krumlauf R. Homeobox genes and axial patterning. Cell. 1992 Jan 24;68(2):283–302. doi: 10.1016/0092-8674(92)90471-n. [DOI] [PubMed] [Google Scholar]
  13. McIntyre A., Gibson P. R., Young G. P. Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut. 1993 Mar;34(3):386–391. doi: 10.1136/gut.34.3.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rabbitts T. H. Translocations, master genes, and differences between the origins of acute and chronic leukemias. Cell. 1991 Nov 15;67(4):641–644. doi: 10.1016/0092-8674(91)90057-6. [DOI] [PubMed] [Google Scholar]
  15. Roberts C. W., Shutter J. R., Korsmeyer S. J. Hox11 controls the genesis of the spleen. Nature. 1994 Apr 21;368(6473):747–749. doi: 10.1038/368747a0. [DOI] [PubMed] [Google Scholar]
  16. Rubin H. Cancer as a dynamic developmental disorder. Cancer Res. 1985 Jul;45(7):2935–2942. [PubMed] [Google Scholar]
  17. Schweinfest C. W., Henderson K. W., Suster S., Kondoh N., Papas T. S. Identification of a colon mucosa gene that is down-regulated in colon adenomas and adenocarcinomas. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4166–4170. doi: 10.1073/pnas.90.9.4166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sigal S. H., Brill S., Fiorino A. S., Reid L. M. The liver as a stem cell and lineage system. Am J Physiol. 1992 Aug;263(2 Pt 1):G139–G148. doi: 10.1152/ajpgi.1992.263.2.G139. [DOI] [PubMed] [Google Scholar]
  19. Uriel J. Cancer, retrodifferentiation, and the myth of Faust. Cancer Res. 1976 Nov;36(11 Pt 2):4269–4275. [PubMed] [Google Scholar]
  20. Wewer U. M., Mercurio A. M., Chung S. Y., Albrechtsen R. Deoxyribonucleic-binding homeobox proteins are augmented in human cancer. Lab Invest. 1990 Oct;63(4):447–454. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES