Skip to main content
SpringerLink
Log in

Inhibin/activin-betaE subunit in normal and malignant human cervical tissue and cervical cancer cell lines

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

Inhibins are dimeric glycoproteins, composed of an alpha-subunit and one of two possible beta-subunits (betaA or betaB), with substantial roles in human reproduction and in endocrine-responsive tumours. Recently a novel beta subunit named betaE was described, although it is still unclear if normal or cancerous cervical epithelial cells as well as cervical cancer cell lines can synthesise the novel inhibin-betaE subunit. About 4 normal cervical tissue samples together with 10 specimens of well-differentiated squamous cervical cancer and adenocarcinoma of the cervix were immunohistochemical analyzed. Additionally, two cervical carcinoma cell lines (HeLa and CaSki) were analyzed by immunofluorescence and RT–PCR for the expression of this novel subunit. We demonstrated for the first time an immunolabelling of the inhibin-betaE subunit in normal and malignant cervical tissue, as well as cervical cancer cells. Although the physiological role is still quite unclear in cervical tissue, inhibin-βE might play important roles in carcinogenesis. Moreover, the synthesis of this subunit in cervical carcinoma cell lines of squamous and glandular epithelial origins also allows the use of these cell lines in elucidating its functions in cervical cancer pathogenesis. However, since the expression of the inhibin-βE is minimal in HeLa cells as assessed by immunofluorescence and RT–PCR, the CaSki cell line might be a better model for further functional experiments regarding cervical cancer pathogenesis.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Beattie GM, Lopez AD, Bucay N, Hinton A, Firpo MT, King CC, Hayek A (2005) Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers. Stem Cells 23:489–495

    Article  CAS  PubMed  Google Scholar 

  • Brüning A, Makovitzky J, Gingelmaier A, Friese K, Mylonas I (2009) The metastasis-associated genes MTA1 and MTA3 are abundantly expressed in human placenta and chorionic carcinoma cells. Histochem Cell Biol 132:33–38

    Article  PubMed  Google Scholar 

  • Chabicovsky M, Herkner K, Rossmanith W (2003) Overexpression of activin beta(C) or activin beta(E) in the mouse liver inhibits regenerative deoxyribonucleic acid synthesis of hepatic cells. Endocrinology 144:3497–3504

    Article  CAS  PubMed  Google Scholar 

  • Chen YG, Lui HM, Lin SL, Lee JM, Ying SY (2002) Regulation of cell proliferation, apoptosis, and carcinogenesis by activin. Exp Biol Med (Maywood) 227:75–87

    CAS  Google Scholar 

  • de Kretser DM, Hedger MP, Loveland KL, Phillips DJ (2002) Inhibins, activins and follistatin in reproduction. Hum Reprod Update 8:529–541

    Article  PubMed  Google Scholar 

  • Fang J, Yin W, Smiley E, Wang SQ, Bonadio J (1996) Molecular cloning of the mouse activin beta E subunit gene. Biochem Biophys Res Commun 228:669–674

    Article  CAS  PubMed  Google Scholar 

  • Franco EL, Schlecht NF, Saslow D (2003) The epidemiology of cervical cancer. Cancer J 9:348–359

    Article  PubMed  Google Scholar 

  • Hashimoto O, Tsuchida K, Ushiro Y, Hosoi Y, Hoshi N, Sugino H, Hasegawa Y (2002) cDNA cloning and expression of human activin betaE subunit. Mol Cell Endocrinol 194:117–122

    Article  CAS  PubMed  Google Scholar 

  • Hötten G, Neidhardt H, Schneider C, Pohl J (1995) Cloning of a new member of the TGF-beta family: a putative new activin beta C chain. Biochem Biophys Res Commun 206:608–613

    Article  Google Scholar 

  • Kimmich T, Brüning A, Käufl SD, Makovitzky J, Kuhn C, Jeschke U, Friese K, Mylonas I (2009) Inhibin/activin-betaC and -betaE subunits in the Ishikawa human endometrial adenocarcinoma cell line. Arch Gynecol Obstet. doi:10.1007/s00404-009-1314-7

  • Lau AL, Nishimori K, Matzuk MM (1996) Structural analysis of the mouse activin beta C gene. Biochim Biophys Acta 1307:145–148

    PubMed  Google Scholar 

  • Lau AL, Kumar TR, Nishimori K, Bonadio J, Matzuk MM (2000) Activin betaC and betaE genes are not essential for mouse liver growth, differentiation, and regeneration. Mol Cell Biol 20:6127–6137

    Article  CAS  PubMed  Google Scholar 

  • Makovitzky J, Radtke A, Shabani N, Friese K, Gerber B, Mylonas I (2009) Invasive hydatidiform mole: immunohistochemical labelling of inhibin/activin subunits, Ki67, p53 and glycodelin A in a rare case. Acta Histochem 111(4):360–365

    Google Scholar 

  • Massad LS, Einstein M, Myers E, Wheeler CM, Wentzensen N, Solomon D (2009) The impact of human papillomavirus vaccination on cervical cancer prevention efforts. Gynecol Oncol 114:360–364

    Article  PubMed  Google Scholar 

  • Matzuk MM, Finegold MJ, Su JG, Hsueh AJ, Bradley A (1992) Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature 360:313–319

    Article  CAS  PubMed  Google Scholar 

  • Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ (2003) Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348:518–527

    Article  PubMed  Google Scholar 

  • Mylonas I, Jeschke U, Wiest I, Hoeing A, Vogl J, Shabani N, Kuhn C, Schulze S, Kupka MS, Friese K (2004) Inhibin/activin subunits alpha, beta-A and beta-B are differentially expressed in normal human endometrium throughout the menstrual cycle. Histochem Cell Biol 122:461–471

    Article  CAS  PubMed  Google Scholar 

  • Mylonas I, Jeschke U, Shabani N, Kuhn C, Friese K, Gerber B (2005a) Inhibin/activin subunits (inhibin-alpha, -betaA and -betaB) are differentially expressed in human breast cancer and their metastasis. Oncol Rep 13:81–88

    CAS  PubMed  Google Scholar 

  • Mylonas I, Makovitzky J, Fernow A, Richter DU, Jeschke U, Briese V, Gerber B, Friese K (2005b) Expression of the inhibin/activin subunits alpha (alpha), beta-A (betaA) and beta-B (betaB) in benign human endometrial polyps and tamoxifen-associated polyps. Arch Gynecol Obstet 272:59–66

    Article  CAS  PubMed  Google Scholar 

  • Mylonas I, Makovitzky J, Hoeing A, Richter DU, Vogl J, Schulze S, Jeschke U, Briese V, Friese K (2006a) Inhibin/activin subunits beta-A (-betaA) and beta-B (-betaB) are differentially localised in normal, hyperplastic and malignant human endometrial tissue. Acta Histochem 108:1–11

    Article  CAS  PubMed  Google Scholar 

  • Mylonas I, Schiessl B, Jeschke U, Vogl J, Makrigiannakis A, Kuhn C, Kunze S, Schulze S, Kainer F, Friese K (2006b) Expression of inhibin/activin subunits alpha (-alpha), beta A (-beta (A)) and beta B (-beta (B)) in placental tissue of normal and intrauterine growth restricted (IUGR) pregnancies. J Mol Histol 37:43–52

    Article  CAS  PubMed  Google Scholar 

  • Mylonas I, Schiessl B, Jeschke U, Vogl J, Makrigiannakis A, Kuhn C, Schulze S, Kainer F, Friese K (2006c) Expression of inhibin/activin subunits alpha (-alpha), betaA (-betaA), and betaB (-betaB) in placental tissue of normal, preeclamptic and HELLP pregnancies. Endocr Pathol 17:19–34

    Article  CAS  PubMed  Google Scholar 

  • Mylonas I, Shabani N, Vogl J, Makovitzky J, Kunze S, Kuhn C, Schulze S, Friese K, Jeschke U (2007) Inhibin/activin subunits are immunohistochemically expressed in complete and partial hydatidiform moles. Anticancer Res 27:1995–2000

    CAS  PubMed  Google Scholar 

  • Mylonas I, Makovitzky J, Shabani N, Gingelmaier A, Dian D, Kuhn C, Schulze S, Kunze S, Jeschke U, Friese K (2009a) Development and characterisation of an antibody for the immunohistochemical detection of inhibin/activin betaE (betaE) in normal human ovarian and placental tissue. Acta Histochem 111:366–371

    PubMed  Google Scholar 

  • Mylonas I, Worbs S, Shabani N, Kuhn C, Kunze S, Schulze S, Dian D, Gingelmaier A, Schindlbeck C, Bruning A, Sommer H, Jeschke U, Friese K (2009b) Inhibin-alpha subunit is an independent prognostic parameter in human endometrial carcinomas: analysis of inhibin/activin-alpha, -betaA and -betaB subunits in 302 cases. Eur J Cancer 45:1304–1314

    Article  CAS  PubMed  Google Scholar 

  • O’Bryan MK, Sebire KL, Gerdprasert O, Hedger MP, Hearn MT, de Kretser DM (2000) Cloning and regulation of the rat activin betaE subunit. J Mol Endocrinol 24:409–418

    Article  PubMed  Google Scholar 

  • Oda S, Nishimatsu S, Murakami K, Ueno N (1995) Molecular cloning and functional analysis of a new activin beta subunit: a dorsal mesoderm-inducing activity in Xenopus. Biochem Biophys Res Commun 210:581–588

    Article  CAS  PubMed  Google Scholar 

  • Petraglia F, Florio P, Luisi S, Gallo R, Gadducci A, Vigano P, Di Blasio AM, Genazzani AR, Vale W (1998) Expression and secretion of inhibin and activin in normal and neoplastic uterine tissues. High levels of serum activin A in women with endometrial and cervical carcinoma. J Clin Endocrinol Metab 83:1194–1200

    Article  CAS  PubMed  Google Scholar 

  • Phillips DJ, de Kretser DM, Hedger MP (2009) Activin and related proteins in inflammation: not just interested bystanders. Cytokine Growth Factor Rev 20:153–164

    Article  CAS  PubMed  Google Scholar 

  • Reis FM, Luisi S, Carneiro MM, Cobellis L, Federico M, Camargos AF, Petraglia F (2004) Activin, inhibin and the human breast. Mol Cell Endocrinol 225:77–82

    Article  CAS  PubMed  Google Scholar 

  • Risbridger GP, Schmitt JF, Robertson DM (2001) Activins and inhibins in endocrine and other tumors. Endocr Rev 22:836–858

    Article  CAS  PubMed  Google Scholar 

  • Risbridger GP, Ball EM, Wang H, Mellor SL, Peehl DM (2004) Re-evaluation of inhibin alpha subunit as a tumour suppressor in prostate cancer. Mol Cell Endocrinol 225:73–76

    Article  CAS  PubMed  Google Scholar 

  • Robertson DM, Pruysers E, Jobling T (2007) Inhibin as a diagnostic marker for ovarian cancer. Cancer Lett 249:14–17

    Article  CAS  PubMed  Google Scholar 

  • Rodgarkia-Dara C, Vejda S, Erlach N, Losert A, Bursch W, Berger W, Schulte-Hermann R, Grusch M (2006) The activin axis in liver biology and disease. Mutat Res 613:123–137

    Article  CAS  PubMed  Google Scholar 

  • Vale W, Rivier C, Hsueh A, Campen C, Meunier H, Bicsak T, Vaughan J, Corrigan A, Bardin W, Sawchenko P et al (1988) Chemical and biological characterization of the inhibin family of protein hormones. Recent Prog Horm Res 44:1–34

    CAS  PubMed  Google Scholar 

  • Vejda S, Cranfield M, Peter B, Mellor SL, Groome N, Schulte-Hermann R, Rossmanith W (2002) Expression and dimerization of the rat activin subunits betaC and betaE: evidence for the ormation of novel activin dimers. J Mol Endocrinol 28:137–148

    Article  CAS  PubMed  Google Scholar 

  • Vejda S, Erlach N, Peter B, Drucker C, Rossmanith W, Pohl J, Schulte-Hermann R, Grusch M (2003) Expression of activins C and E induces apoptosis in human and rat hepatoma cells. Carcinogenesis 24:1801–1809

    Article  CAS  PubMed  Google Scholar 

  • Wada W, Medina JJ, Kuwano H, Kojima I (2005) Comparison of the function of the beta(C) and beta(E) subunits of activin in AML12 hepatocytes. Endocr J 52:169–175

    Article  CAS  PubMed  Google Scholar 

  • Waggoner SE (2003) Cervical cancer. Lancet 361:2217–2225

    Article  PubMed  Google Scholar 

  • Worbs S, Shabani N, Mayr D, Gingelmaier A, Makrigiannakis A, Kuhn C, Jeschke U, Kupka MS, Friese K, Mylonas I (2007) Expression of the inhibin/activin subunits (-alpha, -betaA and -betaB) in normal and carcinogenic endometrial tissue: possible immunohistochemical differentiation markers. Oncol Rep 17:97–104

    CAS  PubMed  Google Scholar 

  • Yoshinaga K, Mimori K, Yamashita K, Utsunomiya T, Inoue H, Mori M (2003) Clinical significance of the expression of activin A in esophageal carcinoma. Int J Oncol 22:75–80

    CAS  PubMed  Google Scholar 

  • Yoshinaga K, Yamashita K, Mimori K, Tanaka F, Inoue H, Mori M (2008) Activin a causes cancer cell aggressiveness in esophageal squamous cell carcinoma cells. Ann Surg Oncol 15:96–103

    Article  PubMed  Google Scholar 

  • Zheng W, Luo MP, Welt C, Lambert-Messerlian G, Sung CJ, Zhang Z, Ying SY, Schneyer AL, Lauchlan SC, Felix JC (1998) Imbalanced expression of inhibin and activin subunits in primary epithelial ovarian cancer. Gynecol Oncol 69:23–31

    Article  CAS  PubMed  Google Scholar 

  • zur Hausen H (2009) Papillomaviruses in the causation of human cancers—a brief historical account. Virology 384:260–265

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Mrs. C. Kuhn, Mrs. S. Kunze, Mrs S. Schulze and Mrs. I. Wiest for their excellent work with cervical tissue samples. Moreover, we express our gratitude to Dr. U. Jeschke and Prof. K. Friese for his help in this study and Mrs. T. Kimmich for the RT–PCR analysis. This study was partially supported by the FöFoLe program of the Ludwig-Maximilians-University Munich (297/03), the Friedrich-Baur-Institute Munich and the Weigland Stipendium Program of the Ludwig-Maximilians-University Munich for I. Mylonas.

Author information

Authors and Affiliations

  1. 1st Department of Obstetrics and Gynaecology, Ludwig-Maximilians-University Munich, Maistrasse 11, 80337, Munich, Germany

    Florian Bergauer, Ansgar Brüning, Naim Shabani, Thomas Blankenstein, Julia Jückstock, Darius Dian & Ioannis Mylonas

  2. Department of Obstetrics and Gynaecology, Klinikum Neuperlach, Munich, Germany

    Naim Shabani

Authors
  1. Florian Bergauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ansgar Brüning
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naim Shabani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas Blankenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Julia Jückstock
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Darius Dian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ioannis Mylonas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ioannis Mylonas.

Additional information

Florian Bergauer and Ansgar Brüning contributed equally.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bergauer, F., Brüning, A., Shabani, N. et al. Inhibin/activin-betaE subunit in normal and malignant human cervical tissue and cervical cancer cell lines. J Mol Hist 40, 353–359 (2009). https://doi.org/10.1007/s10735-009-9246-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-009-9246-x

Keywords

Search

Navigation