Doc-2/hDab2 expression is up-regulated in primary pancreatic cancer but reduced in metastasis.

Abstract

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.

• Authors: Y Huang, H Friess, J Kleeff, I Esposito, Z Zhu, S Liu, S C Mok, A Zimmermann, M W Büchler
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 81 Issue 6 Pg. 863-73 (Jun 2001) ISSN: 0023-6837 [Print] United States
• PMID: 11406647 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Adaptor Proteins, Vesicular Transport
• Apoptosis Regulatory Proteins
• DAB2 protein, human
• Proteins
• RNA, Messenger
• Tumor Suppressor Proteins

Topics

• Adaptor Proteins, Signal Transducing
• Adaptor Proteins, Vesicular Transport
• Adenocarcinoma (metabolism, pathology, secondary)
• Adult
• Aged
• Apoptosis Regulatory Proteins
• Blotting, Northern
• Blotting, Western
• Female
• Genes, Tumor Suppressor
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Male
• Middle Aged
• Pancreas (metabolism)
• Pancreatic Neoplasms (metabolism, pathology, secondary)
• Proteins (genetics, metabolism)
• RNA, Messenger (metabolism)
• Reference Values
• Tumor Cells, Cultured
• Tumor Suppressor Proteins
• Up-Regulation