Differential expression of galectin-3 in pituitary tumors.
Galectin-3 (Gal-3), a beta-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 p27(Kip1) (p27)-null mice, which produce mainly ACTH, showed increased Gal-3 expression levels compared with control mice. Treatment with transforming growth factor beta1, 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 beta1 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.
Department of Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Dominik
D
Riss
Long
L
Jin
Xiang
X
Qian
Jill
J
Bayliss
Bernd W
BW
Scheithauer
William F
WF
Young
Sergio
S
Vidal
Kalman
K
Kovacs
Avraham
A
Raz
Ricardo V
RV
Lloyd
D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016373:DNA, Antisense / Q000235:genetics / Q000494:pharmacology; D018450:Disease Progression; D037502:Galectin 3 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000172:deficiency
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D016373:DNA, Antisense; D037502:Galectin 3; D034741:RNA, Small Interfering; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27