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[Cancer Research 63, 2251-2255, May 1, 2003]
© 2003 American Association for Cancer Research


Tumor Biology

Differential Expression of Galectin-3 in Pituitary Tumors1

Dominik Riss, Long Jin, Xiang Qian, Jill Bayliss, Bernd W. Scheithauer, William F. Young, Jr., Sergio Vidal, Kalman Kovacs, Avraham Raz and Ricardo V. Lloyd2

Department of Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905 [D. R., L. J., X. Q., J. B., B. W. S., W. F. Y., R. V. L.]; Department of Pathology, St. Michaels Hospital, Toronto, Canada [S. V., K. K.]; and Department of Pathology and Tumor Progression and Metastasis Program, Karmanos Cancer Institute Wayne State University School of Medicine, Detroit, Michigan [A. R.]

Galectin-3 (Gal-3), a ß-galactoside-binding protein, has been implicated in a variety of biological functions, including cell proliferation and differentiation, tumor cell adhesion, angiogenesis, apoptosis, tumor progression, and metastasis. We investigated the role of Gal-3 in the development and progression of pituitary tumors. Immunohistochemical and Western blot analysis of normal and neoplastic human pituitaries showed that only lactotroph (PRL) and corticotroph (ACTH) hormone-producing cells and tumors expressed Gal-3. Gal-3 was present in 24 of 38 (63.2%) PRL adenomas, 5 of 6 (83.3%) PRL carcinomas, 19 of 41 (46.3) ACTH adenomas, and 7 of 8 (87.5%) ACTH carcinomas, but not in 112 other pituitary adenomas and carcinomas. Pituitary folliculo-stellate cells, which have macrophage-type functions in the anterior pituitary, also expressed Gal-3. Hyperplastic and neoplastic pituitaries from p27Kip1 (p27)-null mice, which produce mainly ACTH, showed increased Gal-3 expression levels compared with control mice. Treatment with transforming growth factor ß1, which regulates pituitary cell proliferation, reduced Gal-3 as well as p27 expression levels in cultured HP75 pituitary cells and Gal-3 in cultured pituitary cells from p27-null mice, suggesting that p27 is not necessary for the inhibitory effects of transforming growth factor ß1 on the cell cycle in the pituitary. The role of Gal-3 in pituitary cell function was examined by RNA interference experiments. Inhibition of Gal-3 gene expression by RNA interference decreased HP75 cell proliferation and increased apoptosis. These results indicate that Gal-3 has an important role in pituitary cell proliferation and tumor progression.




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