dc.contributor.author |
Elston, Marianne |
en |
dc.contributor.author |
Gill, AJ |
en |
dc.contributor.author |
Conaglen, John |
en |
dc.contributor.author |
Clarkson, A |
en |
dc.contributor.author |
Shaw, JM |
en |
dc.contributor.author |
Law, AJJ |
en |
dc.contributor.author |
Cook, RJ |
en |
dc.contributor.author |
Little, NS |
en |
dc.contributor.author |
Clifton-Bligh, RJ |
en |
dc.contributor.author |
Robinson, BG |
en |
dc.contributor.author |
McDonald, KL |
en |
dc.date.accessioned |
2012-03-30T05:38:00Z |
en |
dc.date.issued |
2008-03-01 |
en |
dc.identifier.citation |
ENDOCRINOLOGY 149(3):1235-1242 01 Mar 2008 |
en |
dc.identifier.issn |
0013-7227 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/16194 |
en |
dc.description.abstract |
The etiology of sporadic pituitary tumors is currently unknown. The Writ pathways have been implicated in the pathogenesis of a variety of human tumors, but the role of these pathways in pituitary tumors is unclear. Microarray analysis using the Affymetrix HG U133 plus 2.0 GeneChips identified four secreted frizzled-related protein (sFRP) family members of Writ pathway inhibitors that were differentially expressed in both nonfunctioning and clinically functioning pituitary tumors (n = 20) compared with normal pituitary controls (n = 3). Reduced tumor expression of Writ inhibitory factor-1 (WIF1), sFRP2, and sFRP4 mRNA was confirmed by real-time quantitative RT-PCR (P < 0.001 and P = 0.002 and 0.013, respectively) in all pituitary subtypes. Hypermethylation of the WIF1 promoter was present in 88% of the pituitary tumors (n = 41). Seventy-six percent of pituitary tumors demonstrated absent or weak cytoplasmic WIF1 staining by immunohistochemistry (n = 41), although preserved staining was seen in some functioning tumors, with strong staining in 92% of normal pituitary controls (n = 13). The Writ pathway target gene cyclin D1 was found to be up-regulated specifically in the nonfunctioning pituitary tumors compared with controls at,; both mRNA and protein level, supportive of activation of the Wnt-beta-catenin pathway. Nuclear accumulation of P-catenin, however, was not observed in any pituitary tumors (n = 70). By transfecting GH3 cells with WIF1, decreased,cell proliferation and colony formation was observed compared with empty vector controls. In conclusion, our data suggest that WIF1 may be a tumor suppressor, specifically in nonfunctioning pituitary tumors, and that the Writ pathways are important in pituitary tumorigenesis. |
en |
dc.language |
English |
en |
dc.publisher |
The Endocrine Society |
en |
dc.relation.ispartofseries |
Endocrinology |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.
Details obtained from http://www.sherpa.ac.uk/romeo/issn/0013-7227/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Science & Technology |
en |
dc.subject |
Life Sciences & Biomedicine |
en |
dc.subject |
Endocrinology & Metabolism |
en |
dc.subject |
HUMAN COLORECTAL-CANCER |
en |
dc.subject |
FACTOR-I |
en |
dc.subject |
BETA-CATENIN |
en |
dc.subject |
EPIGENETIC INACTIVATION |
en |
dc.subject |
PROMOTER HYPERMETHYLATION |
en |
dc.subject |
GENE-EXPRESSION |
en |
dc.subject |
DNA METHYLATION |
en |
dc.subject |
PROSTATE-CANCER |
en |
dc.subject |
BLADDER-CANCER |
en |
dc.subject |
E-CADHERIN |
en |
dc.title |
Wnt pathway inhibitors are strongly down-regulated in pituitary tumors |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1210/en.2007-0542 |
en |
pubs.issue |
3 |
en |
pubs.begin-page |
1235 |
en |
pubs.volume |
149 |
en |
dc.rights.holder |
Copyright: The Endocrine Society |
en |
dc.identifier.pmid |
18079202 |
en |
pubs.end-page |
1242 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
114847 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
School of Medicine |
en |
pubs.org-id |
Medicine Department |
en |
pubs.record-created-at-source-date |
2012-03-30 |
en |
pubs.dimensions-id |
18079202 |
en |