| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cancer Genetics Unit (M.S.E., J.M.S., R.J.C.-B., K.L.M.), Kolling Institute of Medical Research, Department of Anatomical Pathology (A.J.G., A.C.), Royal North Shore Hospital, and Department of Neurosurgery (R.J.C., N.S.L.), Royal North Shore and North Shore Private Hospitals, Sydney, New South Wales 2065, Australia; University of Sydney (A.J.C., A.C.), and Faculty of Medicine (B.G.R.), Sydney, New South Wales 2006, Australia; Department of Endocrinology (J.V.C.), Waikato Hospital, Waikato 3204, New Zealand; and Department of Neurosurgery (A.J.J.L.), Auckland City Hospital, Auckland 1023, New Zealand
Address all correspondence and requests for reprints to: Marianne S. Elston, M.B. Ch.B., Cancer Genetics Unit, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. E-mail: marianne{at}med.usyd.edu.au.
The etiology of sporadic pituitary tumors is currently unknown. The Wnt 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 Wnt 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 Wnt 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 Wnt 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-β-catenin pathway. Nuclear accumulation of β-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 Wnt pathways are important in pituitary tumorigenesis.
This article has been cited by other articles:
 |
|
 |
|
  M. S. Elston, A. J. Gill, J. V. Conaglen, A. Clarkson, R. J. Cook, N. S. Little, B. G. Robinson, R. J. Clifton-Bligh, and K. L. McDonald Nuclear Accumulation of E-Cadherin Correlates with Loss of Cytoplasmic Membrane Staining and Invasion in Pituitary Adenomas J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1436 - 1442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tang, A. R. Simoneau, W.-x. Liao, G. Yi, C. Hope, F. Liu, S. Li, J. Xie, R. F. Holcombe, F. A. Jurnak, et al. WIF1, a Wnt pathway inhibitor, regulates SKP2 and c-myc expression leading to G1 arrest and growth inhibition of human invasive urinary bladder cancer cells Mol. Cancer Ther., February 1, 2009; 8(2): 458 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Payne, S. Maleki, M. Messina, M. G. O'Sullivan, G. Stone, N. R. Hall, J. F. Parkinson, H. R. Wheeler, R. J. Cook, M. T. Biggs, et al. Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma Mol. Cancer Ther., October 1, 2008; 7(10): 3420 - 3428. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
