Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2009-9-2
pubmed:abstractText
Ski used to be defined as an oncogene that contributes to the resistance of tumor cells to transforming growth factor-beta (TGF-beta)-induced growth arrest. As TGF-beta has a dual effect on tumor growth with both tumor-suppressing and -promoting activity depending on the stage of carcinogenesis and the cell type, the precise role of Ski in carcinogenesis remains unclear. In this study, we show that downregulation of Ski through lentivirus-mediated RNA interference decreases tumor growth both in vitro and in vivo, yet promotes cell invasiveness in vitro, and lung metastasis in vivo in the pancreatic cancer cell line SW1990, which contain wild-type Smad4 expression, and the BxPC3 cell line, which is Smad4 deficient. We also show that the downregulation of Ski increases TGF-beta-induced transcriptional activity, which is associated with increased TGF-beta-dependent Smad2/3 phosphorylation, and results in an altered expression profile of TGF-beta-inducible genes involved in metastasis, angiogenesis and cell proliferation and epithelial-mesenchymal transition. Immunohistochemical analysis of specimens from 71 patients with pancreatic adenocarcinoma showed a significant association between overexpression of Ski and decreased patient survival time (P = 0.0024). Our results suggest that Ski may act as a tumor proliferation-promoting factor or as a metastatic suppressor in human pancreatic cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1497-506
pubmed:meshHeading
pubmed-meshheading:19546161-Adenocarcinoma, pubmed-meshheading:19546161-Animals, pubmed-meshheading:19546161-Carcinoma, Pancreatic Ductal, pubmed-meshheading:19546161-Cell Line, Tumor, pubmed-meshheading:19546161-Cell Movement, pubmed-meshheading:19546161-DNA-Binding Proteins, pubmed-meshheading:19546161-Female, pubmed-meshheading:19546161-Humans, pubmed-meshheading:19546161-Lung Neoplasms, pubmed-meshheading:19546161-Mice, pubmed-meshheading:19546161-Mice, Inbred BALB C, pubmed-meshheading:19546161-Neoplasm Invasiveness, pubmed-meshheading:19546161-Pancreatic Neoplasms, pubmed-meshheading:19546161-Prognosis, pubmed-meshheading:19546161-Proto-Oncogene Proteins, pubmed-meshheading:19546161-Signal Transduction, pubmed-meshheading:19546161-Smad Proteins, pubmed-meshheading:19546161-Transforming Growth Factor beta
pubmed:year
2009
pubmed:articleTitle
Dual role of Ski in pancreatic cancer cells: tumor-promoting versus metastasis-suppressive function.
pubmed:affiliation
Department of Hepatobiliary and Pancreatic Oncology, Cancer Hospital, Fudan University, Shanghai 200032, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't