title: A transcriptional repressor of osteopontin expression in the 4T1 murine breast cancer cell line.
abstract: 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.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Chengjiang
authors.initials: C
authors.lastname: Gao
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Mi
authors.forename: Hongtao
authors.initials: H
authors.lastname: Guo
authors.forename: Junping
authors.initials: J
authors.lastname: Wei
authors.forename: Philip Y
authors.initials: PY
authors.lastname: Wai
authors.forename: Paul C
authors.initials: PC
authors.lastname: Kuo
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D053495:Osteopontin; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000235:genetics*; D014162:Transfection
chemical_list: D004273:DNA, Neoplasm; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin