Galectin-3 enhances cyclin D(1) promoter activity through SP1 and a cAMP-responsive element in human breast epithelial cells.
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 D(1) gene expression, a critical inducer of the cell cycle and a potential oncogene in human cancer. We found that galectin-3 induces cyclin D(1) 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 D(1) promoter may result from enhancement/stabilization of nuclear protein-DNA complex formation at the CRE site of the cyclin D(1) promoter. We also show that galectin-3 co-operates with, but does not depend on, pRb for cyclin D(1) promoter activation. The present study reveals a growth promoting activity of galectin-3 through cyclin D(1) induction, and suggests a novel function of nuclear galectin-3 in the regulation of gene transcription.
Lin
Huei-Min
HM
Department of Pathology, Wayne State University, School of Medicine, Detroit, Michigan, MI 48201, USA.
Pestell
Richard G
RG
Raz
Avraham
A
Kim
Hyeong-Reh Choi
HR
D001483:Base Sequence; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D019938:Cyclin D1 / Q000235:genetics*; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000378:metabolism; D037502:Galectin 3 / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000502:physiology*
D017931:DNA Primers; D037502:Galectin 3; D016329:Sp1 Transcription Factor; D019938:Cyclin D1; D000242:Cyclic AMP