Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-6-14
pubmed:abstractText
SUMMARY: DOC-2/hDab2 (DOC-2) has tumor suppressive functions in ovarian cancer and choriocarcinoma. In these tumors, it negatively influences mitogenic signal transduction of growth factors and blocks ras activity. Pancreatic cancer exhibits a high frequency of K-ras gene mutations; however, it is not known whether DOC-2 expression is altered in these tumors. Therefore, we investigated DOC-2 expression in 22 pancreatic adenocarcinomas and in 6 pancreatic cancer cell lines. Findings in human tumors were compared with normal controls and correlated with clinicopathological data. Additionally, the influence of K-ras on DOC-2 transcription was investigated. Northern blot and Western blot analyses both demonstrated an increase of DOC-2 mRNA and protein levels in primary pancreatic cancers in comparison with normal controls. In situ hybridization showed DOC-2 mRNA expression in the majority of cancer cells of primary tumors, as well as in chronic pancreatitis-like lesions surrounding the cancer mass. Immunohistochemistry mirrored the in situ hybridization findings. In contrast, levels of expression of DOC-2 in lymph node metastases were markedly decreased in comparison with levels in primary tumors. In addition, in 5 metastatic pancreatic cancer cell lines, DOC-2 mRNA and protein levels were low, whereas quantitative RT-PCR demonstrated relatively higher levels in a nonmetastatic pancreatic cancer cell line. In conclusion, DOC-2 is overexpressed in primary pancreatic adenocarcinoma but down-regulated in metastatic disease, suggesting a tumor suppressor function of DOC-2 in the late steps of pancreatic carcinogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0023-6837
pubmed:author
pubmed:issnType
Print
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
863-73
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11406647-Adaptor Proteins, Signal Transducing, pubmed-meshheading:11406647-Adaptor Proteins, Vesicular Transport, pubmed-meshheading:11406647-Adenocarcinoma, pubmed-meshheading:11406647-Adult, pubmed-meshheading:11406647-Aged, pubmed-meshheading:11406647-Blotting, Northern, pubmed-meshheading:11406647-Blotting, Western, pubmed-meshheading:11406647-Female, pubmed-meshheading:11406647-Genes, Tumor Suppressor, pubmed-meshheading:11406647-Humans, pubmed-meshheading:11406647-Immunohistochemistry, pubmed-meshheading:11406647-In Situ Hybridization, pubmed-meshheading:11406647-Male, pubmed-meshheading:11406647-Middle Aged, pubmed-meshheading:11406647-Pancreas, pubmed-meshheading:11406647-Pancreatic Neoplasms, pubmed-meshheading:11406647-Proteins, pubmed-meshheading:11406647-RNA, Messenger, pubmed-meshheading:11406647-Reference Values, pubmed-meshheading:11406647-Tumor Cells, Cultured, pubmed-meshheading:11406647-Up-Regulation
pubmed:year
2001
pubmed:articleTitle
Doc-2/hDab2 expression is up-regulated in primary pancreatic cancer but reduced in metastasis.
pubmed:affiliation
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Bern, Switzerland. helmut.friess@insel.ch
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't