Skip to main content
SpringerLink
Log in

Pituitary Tumorigenesis: Role of the Wnt Signaling Pathway

  • Chapter
  • First Online:
Tumors of the Central Nervous System, Volume 10

Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 10))

  • 1325 Accesses

Abstract

Wnt signaling is important in the regulation of normal embryological development of the pituitary gland. Many human tumors have been identified as having altered Wnt signaling and recently the Wnt signaling pathways have also been identified as being perturbed in pituitary adenomas. Whilst data on the presence of nuclear β-catenin, the central mediator of the canonical Wnt signaling pathway, have been conflicting, altered expression of the Wnt signaling pathway inhibitors, WIF1 and members of the SFRP family appear to be common in pituitary adenomas and are likely to contribute to pituitary tumorigenesis. The mechanism by which this occurs is yet to be elucidated but is likely to occur through one of the non-canonical Wnt signaling pathways. Targeting Wnt signaling may prove to be a novel therapeutic option for pituitary tumors. However, due to our incomplete understanding of the roles of the different Wnt pathways in pituitary tumors and the crosstalk between pathways, such therapy needs to be carefully studied due to the potential for unexpected deleterious or long-term consequences.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Altenberger T, Bilban M, Auer M, Knosp E, Wolfsberger S, Gartner W, Mineva I, Zielinski C, Wagner L, Luger A (2006) Identification of DLK1 variants in pituitary- and neuroendocrine tumors. Biochem Biophys Res Commun 340:995–1005

    Article  PubMed  CAS  Google Scholar 

  • Buslei R, Nolde M, Hofmann B, Meissner S, Eyupoglu IY, Siebzehnrubl F, Hahnen E, Kreutzer J, Fahlbusch R (2005) Common mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol (Berl) 109:589–597

    Article  CAS  Google Scholar 

  • Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A (2006) High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 91:4769–4775

    Article  PubMed  CAS  Google Scholar 

  • Elston MS, Clifton-Bligh RJ (2010) Identification of Wnt family inhibitors: a pituitary tumor directed whole genome approach. Mol Cell Endocrinol 326(1–2):48–54

    Article  PubMed  CAS  Google Scholar 

  • Elston MS, Gill AJ, Conaglen JV, Clarkson A, Shaw JM, Law AJ, Cook RJ, Little NS, Clifton-Bligh RJ, Robinson BG, McDonald KL (2008) Wnt pathway inhibitors are strongly down-regulated in pituitary tumors. Endocrinology 149:1235–1242

    Article  PubMed  CAS  Google Scholar 

  • Elston MS, Gill AJ, Conaglen JV, Clarkson A, Cook RJ, Little NS, Robinson BG, Clifton-Bligh RJ, McDonald KL (2009) Nuclear accumulation of e-cadherin correlates with loss of cytoplasmic membrane staining and invasion in pituitary adenomas. J Clin Endocrinol Metab 94:1436–1442

    Article  PubMed  CAS  Google Scholar 

  • Giles A, Madec F, Friedrichsen S, Featherstone K, Chambers T, Harper CV, Resch J, Brabant G, Davis JR (2011) Wnt signaling in estrogen-induced lactotroph proliferation. J Cell Sci 124:540–547

    Article  PubMed  CAS  Google Scholar 

  • He B, Reguart N, You L, Mazieres J, Xu Z, Lee AY, Mikami I, McCormick F, Jablons DM (2005) Blockade of Wnt-1 signaling induces apoptosis in human colorectal cancer cells containing downstream mutations. Oncogene 24:3054–3058

    Article  PubMed  CAS  Google Scholar 

  • Hibberts NA, Simpson DJ, Bicknell JE, Broome JC, Hoban PR, Clayton RN, Farrell WE (1999) Analysis of cyclin D1 (CCND1) allelic imbalance and overexpression in sporadic human pituitary tumors. Clin Cancer Res 5:2133–2139

    PubMed  CAS  Google Scholar 

  • Jessen JR (2009) Noncanonical Wnt signaling in tumor progression and metastasis. Zebrafish 6:21–28

    Article  PubMed  CAS  Google Scholar 

  • Jiang Z, Gui S, Zhang Y (2010) Analysis of differential gene expression by fiber-optic BeadArray and pathway in prolactinomas. Endocrine 38:360–368

    Article  PubMed  CAS  Google Scholar 

  • Lee CI, Hsu MY, Chou CH, Wang C, Lo YS, Loh JK, Howng SL, Hong YR (2009) CTNNB1 (beta-catenin) mutation is rare in brain tumours but involved as a sporadic event in a brain metastasis. Acta Neurochir (Wien) 151:1107–1111

    Article  Google Scholar 

  • Maher MT, Flozak AS, Hartsell AM, Russell S, Beri R, Peled ON, Gottardi CJ (2009) Issues associated with assessing nuclear localization of N-terminally unphosphorylated beta-catenin with monoclonal antibody 8E7. Biol Direct 4:5

    Article  PubMed  Google Scholar 

  • Mazieres J, He B, You L, Xu Z, Lee AY, Mikami I, Reguart N, Rosell R, McCormick F, Jablons DM (2004) Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer. Cancer Res 64:4717–4720

    Article  PubMed  CAS  Google Scholar 

  • Miyakoshi T, Takei M, Kajiya H, Egashira N, Takekoshi S, Teramoto A, Osamura RY (2008) Expression of Wnt4 in human pituitary adenomas regulates activation of the beta-catenin-independent pathway. Endocr Pathol 19:261–273

    Article  PubMed  CAS  Google Scholar 

  • Moreno CS, Evans CO, Zhan X, Okor M, Desiderio DM, Oyesiku NM (2005) Novel molecular signaling and classification of human clinically nonfunctional pituitary adenomas identified by gene expression profiling and proteomic analyses. Cancer Res 65:10214–10222

    Article  PubMed  CAS  Google Scholar 

  • Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275:1787–1790

    Article  PubMed  CAS  Google Scholar 

  • Morris DG, Musat M, Czirjak S, Hanzely Z, Lillington DM, Korbonits M, Grossman AB (2005) Differential gene expression in pituitary adenomas by oligonucleotide array analysis. Eur J Endocrinol 153:143–151

    Article  PubMed  CAS  Google Scholar 

  • Neto AG, McCutcheon IE, Vang R, Spencer ML, Zhang W, Fuller GN (2005) Elevated expression of p21 (WAF1/Cip1) in hormonally active pituitary adenomas. Ann Diagn Pathol 9:6–10

    Article  PubMed  Google Scholar 

  • Nusse R, Varmus HE (1982) Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31:99–109

    Article  PubMed  CAS  Google Scholar 

  • Oikonomou E, Barreto DC, Soares B, De Marco L, Buchfelder M, Adams EF (2005) Beta-catenin mutations in craniopharyngiomas and pituitary adenomas. J Neurooncol 73:205–209

    Article  PubMed  CAS  Google Scholar 

  • Potok MA, Cha KB, Hunt A, Brinkmeier ML, Leitges M, Kispert A, Camper SA (2008) WNT signaling affects gene expression in the ventral diencephalon and pituitary gland growth. Dev Dyn 237:1006–1020

    Article  PubMed  CAS  Google Scholar 

  • Qian ZR, Li CC, Yamasaki H, Mizusawa N, Yoshimoto K, Yamada S, Tashiro T, Horiguchi H, Wakatsuki S, Hirokawa M, Sano T (2002) Role of E-cadherin, alpha-, beta-, and gamma-catenins, and p120 (cell adhesion molecules) in prolactinoma behavior. Mod Pathol 15:1357–1365

    Article  PubMed  Google Scholar 

  • Rubin JS, Barshishat-Kupper M, Feroze-Merzoug F, Xi ZF (2006) Secreted WNT antagonists as tumor suppressors: pro and con. Front Biosci 11:2093–2105

    Article  PubMed  CAS  Google Scholar 

  • Semba S, Han SY, Ikeda H, Horii A (2001) Frequent nuclear accumulation of beta-catenin in pituitary adenoma. Cancer 91:42–48

    Article  PubMed  CAS  Google Scholar 

  • Shorts-Cary L, Xu M, Ertel J, Kleinschmidt-Demasters BK, Lillehei K, Matsuoka I, Nielsen-Preiss S, Wierman ME (2007) Bone morphogenetic protein and retinoic acid-inducible neural specific protein-3 is expressed in gonadotrope cell pituitary adenomas and induces proliferation, migration, and invasion. Endocrinology 148:967–975

    Article  PubMed  CAS  Google Scholar 

  • Sun C, Yamato T, Kondo E, Furukawa T, Ikeda H, Horii A (2005) Infrequent mutation of APC, AXIN1, and GSK3B in human pituitary adenomas with abnormal accumulation of CTNNB1. J Neurooncol 73:131–134

    Article  PubMed  CAS  Google Scholar 

  • Taniguchi H, Yamamoto H, Hirata T, Miyamoto N, Oki M, Nosho K, Adachi Y, Endo T, Imai K, Shinomura Y (2005) Frequent epigenetic inactivation of Wnt inhibitory factor-1 in human gastrointestinal cancers. Oncogene 24:7946–7952

    Article  PubMed  CAS  Google Scholar 

  • Treier M, Gleiberman AS, O’Connell SM, Szeto DP, McMahon JA, McMahon AP, Rosenfeld MG (1998) Multistep signaling requirements for pituitary organogenesis in vivo. Genes Dev 12:1691–1704

    Article  PubMed  CAS  Google Scholar 

  • Tziortzioti V, Ruebel KH, Kuroki T, Jin L, Scheithauer BW, Lloyd RV (2001) Analysis of beta-catenin mutations and alpha-, beta-, and gamma-catenin expression in normal and neoplastic human pituitary tissues. Endocr Pathol 12:125–136

    Article  PubMed  CAS  Google Scholar 

  • Wang DG, Johnston CF, Atkinson AB, Heaney AP, Mirakhur M, Buchanan KD (1996) Expression of bcl-2 oncoprotein in pituitary tumours: comparison with c-myc. J Clin Pathol 49:795–797

    Article  PubMed  CAS  Google Scholar 

  • Xu B, Sano T, Yoshimoto K, Yamada S (2002) Downregulation of E-cadherin and its undercoat proteins in pituitary growth hormone cell adenomas with prominent fibrous bodies. Endocr Pathol 13:341–351

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, Melmed S (1999) Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab 84:761–767

    Article  PubMed  CAS  Google Scholar 

  • Zhou C, Liu S, Zhou X, Xue L, Quan L, Lu N, Zhang G, Bai J, Wang Y, Liu Z, Zhan Q, Zhu H, Xu N (2005) Overexpression of human pituitary tumor transforming gene (hPTTG), is regulated by beta-catenin /TCF pathway in human esophageal squamous cell carcinoma. Int J Cancer 113:891–898

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, Waikato Hospital, Private Bag 3200, Hamilton, Waikato, 3240, New Zealand

    Marianne S. Elston

Authors
  1. Marianne S. Elston
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marianne S. Elston .

Editor information

Editors and Affiliations

  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Elston, M.S. (2013). Pituitary Tumorigenesis: Role of the Wnt Signaling Pathway. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 10. Tumors of the Central Nervous System, vol 10. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5681-6_20

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-5681-6_20

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-007-5680-9

  • Online ISBN: 978-94-007-5681-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation