Galectin-3 enhances cyclin D₁ 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 premRNA 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.