A transcriptional repressor of osteopontin expression in the 4T1 murine breast cancer cell line.

Journal Article

Osteopontin (OPN) is a highly hydrophilic and negatively charged sialoprotein of approximately 298 amino acids which is an important mediator of tumor metastatic behavior. We have previously demonstrated that endotoxin-dependent OPN gene transcription is regulated by a constitutive transcriptional repressor protein, heterogeneous nuclear ribonucleoprotein A/B (hnRNP-A/B). However, in the context of cancer, the role of hnRNP-A/B in the transcriptional regulation of OPN and its metastasis-promoting functions has not been previously studied. We examined hnRNP-A/B in the 4T1 murine mammary epithelial tumor cell line, a thioguanine resistant subline which closely mimics stage IV breast cancer in humans. Our data indicate that hnRNP-A/B p37 binds to the OPN promoter, significantly decreases OPN promoter activity and mRNA levels, ablates OPN protein expression, and inhibits OPN dependent in vitro correlates of metastatic behavior, motility, and invasion. These results are unique and may suggest new therapies to re-establish loco-regional control of cancers.

Full Text

Duke Authors

Cited Authors

  • Gao, C; Mi, Z; Guo, H; Wei, J; Wai, PY; Kuo, PC

Published Date

  • September 3, 2004

Published In

Volume / Issue

  • 321 / 4

Start / End Page

  • 1010 - 1016

PubMed ID

  • 15358129

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2004.07.063

Language

  • eng

Conference Location

  • United States