Clusterin as a biomarker in murine and human intestinal neoplasia.
Early detection of colorectal cancer is critical for the management of this disease. Biomarkers for early detection of several cancers have been developed and applied clinically in recent years. We have sought to discover candidate biomarkers without the restricted choice of markers placed on microarrays, and without the biological complications of genetic and environmental heterogeneity. We have compared by cDNA subtraction two genetically matched sets of mice, one developing multiple intestinal neoplasia (C57BL/6J-ApcMin) and the other tumor-free (C57BL/6J). One prominent candidate biomarker, clusterin, was then subjected to a series of validation steps. In situ hybridization and immunohistochemistry were used to analyze clusterin expression at a cellular level on a series of murine intestinal and human colonic neoplasms. Elevated clusterin expression was characterized within certain regions of murine and human tumors regardless of tumor stage, location, or mode of initiation. The cells showing high clusterin levels generally lacked differentiation markers and adenomatous polyposis coli antigen. Tumor cells undergoing apoptosis expressed low levels of clusterin. Its specific expression patterns and correlation with cellular events during tumorigenesis make it a useful diagnostic tool in the mouse and a potential contributor to the set of biomarkers for early detection of human colon cancer.
Chen
Xiaodi
X
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706, USA.
Halberg
Richard B
RB
Ehrhardt
William M
WM
Torrealba
Jose
J
Dove
William F
WF
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor; D002454:Cell Differentiation; D002455:Cell Division; D051152:Clusterin; D003110:Colonic Neoplasms / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005038:Ethylnitrosourea / Q000494:pharmacology; D005838:Genotype; D006023:Glycoproteins / Q000096:biosynthesis* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007414:Intestinal Neoplasms / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism
D000477:Alkylating Agents; D014408:Biomarkers, Tumor; C495242:CLU protein, human; C495243:Clu protein, mouse; D051152:Clusterin; D018076:DNA, Complementary; D006023:Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D005038:Ethylnitrosourea