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Down-Regulation of DOC-2 in Colorectal Cancer Points to Its Role as a Tumor Suppressor in This Malignancy

Kleeff, Jörg, Huang, Yong, Mok, Samuel C., Zimmermann, Arthur, Friess, Helmut, Büchler, Markus W.·2002·Diseases of the Colon & Rectum
DOI 10.1007/s10350-004-6399-2
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Abstract

Purpose Colorectal cancer is the second most common cause of cancer death and the fourth most prevalent carcinoma in the Western world. Loss of tumor-suppressor gene function in colon cancer leads to ineffective negative growth regulation that is normally exerted by growth-suppressing factors. DOC-2/hDAB2 is a newly identified candidate tumor-suppressor gene in ovarian cancer and choriocarcinoma. In these tumors it negatively influences mitogenic signal transduction of growth factors and blocks ras activity. In the present study we sought to determine the role of DOC-2 in colorectal cancer. Methods DOC-2 expression was analyzed by Northern blot analysis, hybridization, and immunohistochemistry in 27 primary and metastatic colorectal cancers and in 15 normal colon tissues in correlation with clinicopathologic data. Results Northern blot analysis demonstrated a decrease of DOC-2 messenger RNA levels in primary and metastatic colorectal cancers compared with normal controls. In normal colorectal tissues, DOC-2 immunoreactivity was strongly present on the surface columnar epithelial cells. In contrast, DOC-2 immunoreactivity was weak to moderate in the epithelium of colorectal cancers, and the intensity of the signals in colorectal cancer was greatly decreased compared with the normal colorectal tissues. In addition, DOC-2 immunoreactivity in lymph node and liver metastasis was weak to absent in the cancer cells and significantly decreased compared with their primary tumors. Conc…

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  • To date, Dab2 expression has been reported to be reduced or lost in many additional cancer types, including colon, prostate, esophageal, nasopharyngeal, and head and neck.

    “To date, Dab2 expression has been reported to be reduced or lost in many additional cancer types, including colon (Kleeff et al., 2002), prostate (Tseng et al., 1998), esophageal (Anupam et al., 2006), nasopharyngeal (Tong et al., 2010), and head and neck (Hannigan et al., 2010).”

    From Endocytosis and Physiology: Insights from Disabled-2 Deficient Mice (2016) · cites this paper as Kleeff et al., 2002

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Metadata

Authors
Kleeff, J., Huang, Y., Mok, S. C., Zimmermann, A., Friess, H., & Büchler, M. W.
Venue
Diseases of the Colon & Rectum
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2002-09
Volume
45
Issue
9
Pages
1242-1248
ISSN
0012-3706
DOI
10.1007/s10350-004-6399-2
Cited by
42
References
0
Language
en

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