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[Cancer Research 60, 6794-6799, December 15, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

The Expression of the Antiproliferative Gene ZAC Is Lost or Highly Reduced in Nonfunctioning Pituitary Adenomas1

Uberto Pagotto2, 3, Thomas Arzberger2, Marily Theodoropoulou, Yvonne Grübler, Colette Pantaloni, Wolfgang Saeger, Marco Losa, Laurent Journot, Günter K. Stalla4 and Dietmar Spengler4

Max Planck Institute of Psychiatry, 80804 Munich, Germany [U. P., T. A., M. T., Y. G., G. K. S., D. S.]; UPR 9023 CNRS, Mécanismes Moléculaires des Communications Cellulaires, CCIPE, 34094 Montpellier Cedex 05, France [C. P., L. J.]; Institute of Pathology Marienkrankenhaus, 22087 Hamburg, Germany [W. S.]; and Neurosurgical Department, Hospital San Raffaele, 20132 Milan, Italy [M. L.]

The ZAC gene encodes a new zinc-finger protein that concomitantly induces apoptosis and cell cycle arrest and localizes to chromosome 6q24-q25, a well-known hot spot related to cancer. ZAC is highly expressed in the anterior pituitary gland, and its ablation by antisense targeting promotes pituitary cell proliferation. Here we investigate ZAC status in pituitary tumors to evaluate its role in pituitary tumorigenesis. Interestingly, a strong reduction or absence of ZAC mRNA and protein expression was detected in nonfunctioning pituitary adenomas, whereas in clinically active pituitary neoplasias, the decrease in ZAC expression was variable. Loss of expression was not associated with a mutation of the ZAC gene. Our observations suggest that alternative mechanisms of gene inactivation and/or altered regulation of the ZAC gene occur in nonfunctioning pituitary adenomas.




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