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Galectin-3 enhances cyclin D1 promoter activity through SP1 and a cAMP-responsive element in human breast epithelial cells

Oncogene volume 21, pages 8001–8010 (2002)Cite this article

Abstract

Galectin-3 is a multifunctional carbohydrate-binding protein found in the nucleus, cytoplasm and the extracellular milieu. Nuclear galectin-3 expression is associated with cell proliferation, and its role in pre-mRNA splicing has been suggested. In this report, we investigated the role of galectin-3 on cyclin D1 gene expression, a critical inducer of the cell cycle and a potential oncogene in human cancer. We found that galectin-3 induces cyclin D1 promoter activity in human breast epithelial cells independent of cell adhesion through multiple cis-elements, including the SP1 and CRE sites. We present evidence that galectin-3 induction of the cyclin D1 promoter may result from enhancement/stabilization of nuclear protein-DNA complex formation at the CRE site of the cyclin D1 promoter. We also show that galectin-3 co-operates with, but does not depend on, pRb for cyclin D1 promoter activation. The present study reveals a growth promoting activity of galectin-3 through cyclin D1 induction, and suggests a novel function of nuclear galectin-3 in the regulation of gene transcription.

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Abbreviations

The abbreviations used are: PBS:

phosphate-buffered saline

CDK:

cyclin-dependent kinase

CRE:

cAMP-responsive element

CREB:

cAMP-responsive element binding protein

SDS:

sodium dodecyl sulfate

PMSF:

phenylmethylsulfonyl fluoride

IPTG:

isopropylthio-β-D-galactoside

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Acknowledgements

We thank Dr Fei Yu, Dr Kamiar Moin and Ms Linda Mayernik for helping with confocal microscopic analysis, and Dr Xu-Wen Liu, Dr Ki-Kyung Jung, and Ms Mary Ann Krug for helping with the preparation of the manuscript. Supported in part by NIH/NCI (CA-64139) and DOD (DAMD17-99-1-9442) grants to H-RC Kim, and NIH/NCI (CA-46120) to AR.

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  1. Huei-Min Lin

    Present address: Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, 20892-4255, Maryland, MD, USA

Authors and Affiliations

  1. Department of Pathology, Wayne State University, School of Medicine, Detroit, 48201, Michigan, MI, USA

    Huei-Min Lin & Hyeong-Reh Choi Kim

  2. Breast Cancer Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, 48201, Michigan, MI, USA

    Avraham Raz & Hyeong-Reh Choi Kim

  3. Department of Medicine and Developmental and Molecular Biology, The Albert Einstein Cancer Center, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, 10461, New York, NY, USA

    Richard G Pestell

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Correspondence to Hyeong-Reh Choi Kim.

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Lin, HM., Pestell, R., Raz, A. et al. Galectin-3 enhances cyclin D1 promoter activity through SP1 and a cAMP-responsive element in human breast epithelial cells. Oncogene 21, 8001–8010 (2002). https://doi.org/10.1038/sj.onc.1205820

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