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PMID: 19020999 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

RUNX1 and RUNX2 upregulate Galectin-3 expression in human pituitary tumors.

Endocrine ·Vol. 35 ·No. 1 ·2009-02-00 ·Pages 101-11

Zhang HY, Jin L, Stilling GA, Ruebel KH, Coonse K, Tanizaki Y, Raz A, Lloyd RV

Abstract

Galectin-3 is expressed in a cell-type specific manner in human pituitary tumors and may have a role in pituitary tumor development. In this study, we hypothesized that Galectin-3 is regulated by RUNX proteins in pituitary tumors. Transcription factor prediction programs revealed several putative binding sites in the LGALS3 (Galectin-3 gene) promoter region. A human pituitary cell line HP75 was used as a model to study LGALS3 and RUNX interactions using Chromatin immunoprecipitation assay and electrophoresis mobility shift assay. Two binding sites for RUNX1 and one binding site for RUNX2 were identified in the LGALS3 promoter region. LGALS3 promoter was further cloned into a luciferase reporter, and the experiments showed that both RUNX1 and RUNX2 upregulated LGALS3. Knock-down of either RUNX1 or RUNX2 by siRNA resulted in a significant downregulation of Galectin-3 expression and decreased cell proliferation in the HP 75 cell line. Immunohistochemistry showed a close correlation between Galectin-3 expression and RUNX1/RUNX2 level in pituitary tumors. These results demonstrate a novel binding target for RUNX1 and RUNX2 proteins and suggest that Galectin-3 is regulated by RUNX1 and RUNX2 in human pituitary tumor cells by direct binding to the promoter region of LGALS3 and thus may contribute to pituitary tumor progression.

MeSH Terms
Adenoma/genetics,metabolism Cell Proliferation/drug effects Core Binding Factor Alpha 1 Subunit/antagonists & inhibitors,genetics,metabolism,physiology Core Binding Factor Alpha 2 Subunit/antagonists & inhibitors,genetics,metabolism,physiology Disease Progression Galectin 3/genetics,metabolism Gene Expression Regulation, Neoplastic/drug effects HeLa Cells Humans Pituitary Neoplasms/genetics,metabolism Promoter Regions, Genetic Protein Binding RNA, Small Interfering/pharmacology Tumor Cells, Cultured Up-Regulation/drug effects,physiology
Chemicals
Core Binding Factor Alpha 1 Subunit Core Binding Factor Alpha 2 Subunit Galectin 3 RNA, Small Interfering RUNX1 protein, human RUNX2 protein, human
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Zhang He-Yu
Department of Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Jin Long
Stilling Gail A
Ruebel Katharina H
Coonse Kendra
Tanizaki Yoshinori
Raz Avraham
Lloyd Ricardo V
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Article Info
Journal
Endocrine
Abbr.
Endocrine
ISSN
1355-008X
DOI
10.1007/s12020-008-9129-z
Published
2009-02-00
Epub
2008-00-20
Pages
101-11
Language
English
Region
United States
NLM ID
9434444
PMCID
PMC2927870
Subset
IM
Grants
NCI NIH HHS · R37 CA046120-19 · United States
NCI NIH HHS · R37 CA046120 · United States
NCI NIH HHS · R01 CA090249 · United States
NCI NIH HHS · R37CA46120-19 · United States
NCI NIH HHS · CA90249 · United States
External Links
PubMed source DOI: 10.1007/s12020-008-9129-z PMC Full Text View journal details
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