Skip to main content
SpringerLink
Log in

Distribution of Estrogen Receptor Subtypes, Expression of Their Variant Forms, and Clinicopathological Characteristics of Human Colorectal Cancer

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

We examined the expression of estrogen receptor (ER) messenger RNAs (ER-α, ER-β, and ER-β isoforms) in colorectal tumor samples and corresponding normal mucosa, paying particular attention exons 3 and 5 of both ER mRNA subtypes that likely suffer deletions, and may encode proteins that have lost either DNA- or ligand-binding moieties. Then we correlated these findings with the clinicopathological properties of the tumors. Our results demonstrated that in all patients the two ER subtype mRNAs were coexpressed in wild-type form. In 10% of the patients the ER-α mRNA was also present as an exon-5-deleted form that encoded any aberrant protein. Immunohistochemical analysis revealed that the ER-β protein was present in tumor stroma, but not in infiltrating lymphocytes. ER-β1 and ER-β2, isoforms of ER-β, were up-regulated in malignant tissues, whereas the ER-β5 isoform, was found to be equally expressed, at very low levels, in the two tissue compartments. No correlations between ER levels and clinicopathological parameters were found. This suggests that the ER-β mRNA levels are independent of the tumor characteristics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Troisi R, Schairer C, Chow WH, Schatzkin A, Brinton LA, Fraumeni JF Jr: A prospective study of menopausal hormones and risk of colorectal cancer (United States). Cancer causes control 8:130–138, 1997

    Google Scholar 

  2. Grodstein F, Newcomb PA, Stampfer MJ: Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis. Am J Med 106:574–582, 1999

    Google Scholar 

  3. Prihartono N, Palmer JR, Louik C, Shapiro S, Rosenberg L: A case-control study of use of postmenopausal female hormone supplements in relation to the risk of large bowel cancer. Cancer Epidemiol Biomark Prev 9:443–447, 2000

    Google Scholar 

  4. Di Leo A, Messa C, Cavallini A, Linsalata M: Estrogen and colorectal cancer. Curr Drug Targets—Immune, Endocrine Metab Disor 1:1–12, 2001

    Google Scholar 

  5. Francavilla A, Di Leo A, Polimeno L, Conte D, Barone M, Fanizza G, Chiumarulo C, Rizzo G, Rubino M: Nuclear and cytosolic estrogen receptors in human colon carcinoma and in surrounding noncancerous colonic tissue. Gastroenterology 93:1301–1306, 1987

    Google Scholar 

  6. Mosselman S, Polman J, Dijkema R: ERβ: identification and characterization of a novel oestrogen receptor. FEBS Lett 392:49–53, 1996

    Google Scholar 

  7. Vladusic EA, Hornby AE, Guerra-Vlasudic FK, Lupu R: Expression of estrogen receptor β messenger RNA variant in breast cancer. Cancer Res 58:210–214, 1998

    Google Scholar 

  8. Speirs V, Adams IP, Walton DS, Atkin SL: Identification of wild-type and exon 5 deletion variants of estrogen receptor β in normal human mammary gland. J Clin Endocrinol Metab 85:1601–1605, 2000

    Google Scholar 

  9. Gallacchi P, Schoumacher F, Eppenberger-Castori S, von Landenberg EM, Kueng W, Eppenberger U, Mueller H: Increased expression of estrogen-receptor exon-5-deletion variant in relapse tissues of human breast cancer. Int J Cancer 79:44–48, 1998

    Google Scholar 

  10. Lu B, Leygue E, Dotzlaw H, Murphy LJ, Murphy LC, Watson PH: Estrogen receptor-β mRNA variants in human and murine tissues. Mol Cell Endocrinol 138:199–203, 1998

    Google Scholar 

  11. Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, Nordenskjold M, Gustafsson J: Human estrogen receptor β-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab 82:4258–4265, 1997

    Google Scholar 

  12. Brandenberger AW, Tee MK, Lee JY, Chao V, Jaffe RB: Tissue distribution of estrogen receptor α (ERα) and estrogen receptor β (ERβ) messenger RNA in the midgestational human fetus. J Clin Endocrinol Metab 82:3509–3512, 1997

    Google Scholar 

  13. Moore JT, McKee DD, Slentz-Kesler K, Moore LB, Jones SA, Horne EL, Su J, Kliewer SA, Lehmann JM, Willson TM: Cloning and characterization of human oestrogen receptor isoforms. Biochem Biophys Res Commun 247:75–78, 1998

    Google Scholar 

  14. Foley EF, Jazaeri AA, Shupnik MA, Jazaeri O, Rice LW: Selective loss of estrogen receptor β in malignant human colon. Cancer Res 60:245–248, 2000

    Google Scholar 

  15. Campbell-Thompson M, Lynch IJ, Bhardwaj B: Expression of estrogen receptor (ER) subtypes and ERβ isoforms in colon cancer. Cancer Res 61:632–640, 2001

    Google Scholar 

  16. Fiorelli G, Picariello L, Martineti V, Tonelli F, Brandi ML: Functional estrogen receptor β in colon cells. Biochem Biophys Res Commun 261:521–527, 1999

    Google Scholar 

  17. Green GL, Gilna P, Waterfield H, Baker A, Hort Y, Shine J: Sequence and expression of human estrogen receptor complementary DNA. Science, 231:1150–1154, 1986

    Google Scholar 

  18. Leygue E, Dotzlaw H, Watson PH, Murphy LC: Altered estrogen receptor α and β messenger RNA expression during human breast tumorigenesis. Cancer Res 58:3197–3201, 1998

    Google Scholar 

  19. Villa E, Dugani A, Moles A, Capellini L, Grottola A, Buttafoco P, Merighi A, Ferretti I, Esposito P, Miglioli L, Bagni A, Troisi R, DE Hemptinne B, Praet M, Callea F, Vanenti F: Variant liver estrogen receptor transcripts already occur at an early stage of chronic liver disease. Hepatology 27:983–988, 1998

    Google Scholar 

  20. Madsen MW, Reiter BE, Larsen SS, Briand P, Lykkesfeldt AE: Estrogen receptor messenger RNA splice variants are not involved in antiestrogen resistance in sublines of MCF-7 human breast cancer cells. Cancer Res 57:585–589, 1997

    Google Scholar 

  21. Ohlsson H, Lykkesfeldt AE, Madsen MW, Briand P: The estrogen receptor variant lacking exon 5 has dominant negative activity in the human breast epithelial cell line HMT-352251. Cancer Res 58:4264–4268, 1998

    Google Scholar 

  22. Witte D, Chirala M, Younes A, Li Y, Younes M: Estrogen receptor β is expressed in human colorectal adenocarcinoma. Hum Pathol 32:940–944, 2001

    Google Scholar 

  23. Di Leo A, Messa C, Russo F, Misciagna G, Guerra V, Taveri R, Leo S: Prognostic value of cytosolic estrogen receptors in human colorectal carcinoma and surrounding mucosa. Dig Dis Sci 39:2038–2042, 1994

    Google Scholar 

  24. Singh S, Sheppard MC, Langman MJS: Sex differences in the incidence of colorectal cancer: an exploration of oestrogen and progesterone receptors. Gut 34:611–615, 1993

    Google Scholar 

  25. Oshima CT, Wonraht DR, Catarino RM, Maltos D, Forones NM: Estrogen and progesterone receptors in gastric and colorectal cancer. Hepato-Gastroenterol 46:3155–3158, 1999.

    Google Scholar 

  26. Slattery ML, Samowitz WS, Holden JA: Estrogen and progesterone receptors in colon tumors. Am J Clin Pathol 113:364–368, 2000.

    Google Scholar 

  27. Leygue ER, Watson PH, Murphy LC: Estrogen-receptor variants in normal human mammary tissue. J Natl Cancer Inst 88:284–290, 1996

    Google Scholar 

  28. Iwao K, Miyoshi Y, Egawa C, Ikeda N, Noguchi S: Quantitative analysis of estrogen receptor-β mRNA and its variants in human breast cancers. Int J Cancer 88:733–736, 2000

    Google Scholar 

  29. Tong D, Shuster E, Seifert M, Czerwenka K, Leodolte S, Zeillinger R: Expression of estrogen receptor beta isoforms in human breast cancer tissues and cell lines. Breast Cancer Res Treat 71:249–255, 2002.

    Google Scholar 

  30. Krishnamurthy S, Sneige N: Molecular and biologic markers of premalignant lesions of human breast. Adv Anat Pathol 9:185–197, 2002.

    Google Scholar 

  31. Allred DC, Mohsi SK, Fuqua SAW: Histological and biological evolution of human premalignant breast disease. Endocr Relat Cancer 8:47–61, 2001.

    Google Scholar 

  32. Leygue E, Dotzlaw H, Watson PH, Murphy LC: Expression of oestrogen receptor β1, β2, and β5 messenger RNAs in human breast tissue. Cancer Res 59:1175–1179, 1999

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Biochemistry, “S. de Bellis,” Scientific Institute for Digestive Diseases, Via Della Resistenza, 70013-, Castellana Grotte (BA), Italy

    Aldo Cavallini, Caterina Messa, Maria Pricci & Alfredo Di Leo

  2. Laboratory of Pathology I.R.C.C.S. “S. de Bellis,”, Scientific Institute for Digestive Diseases, Via Della Resistenza, 70013-, Castellana Grotte (BA), Italy

    Maria Lucia Caruso

  3. D.E.T.O., University of Bari, Bari, Italy

    Michele Barone

Authors
  1. Aldo Cavallini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Caterina Messa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Pricci
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Lucia Caruso
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michele Barone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alfredo Di Leo
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cavallini, A., Messa, C., Pricci, M. et al. Distribution of Estrogen Receptor Subtypes, Expression of Their Variant Forms, and Clinicopathological Characteristics of Human Colorectal Cancer. Dig Dis Sci 47, 2720–2728 (2002). https://doi.org/10.1023/A:1021053105096

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1021053105096

Search

Navigation