Increased pontin expression in human colorectal cancer tissue.
Wnt signaling plays a fundamental role in the control of cell proliferation and differentiation and is frequently deregulated in colorectal carcinoma leading to an enhanced expression of Wnt target genes. Pontin, a member of the AAA(+) superfamily, has previously been shown to interact with beta-catenin and to enhance TCF/beta-catenin-mediated transcription of Wnt target genes and thus may contribute to carcinogenesis. Here, we studied the expression of pontin in 34 patients with histologically proven colorectal cancer by immunohistochemistry on paraffin-embedded colorectal cancer samples using the monoclonal mouse anti-pontin (5G3-11) antibody. Cytoplasmic pontin staining of tumor cells was present in all cases and was stronger in 84.6% and equal in 15.4% of the cases compared with normal mucosa. In 50% of tumor specimens, an additional nuclear pontin staining pattern was noted with positivity ranging from 10% to 60% of the nuclei. Interestingly, all cases with nuclear pontin expression also revealed nuclear beta-catenin localization. Furthermore, pontin staining was stronger at the invasive margin and in tumor buds than in the tumor center in 41.2% and 37.9% of the cases, respectively. In this context, 66.7% and 64.7% of the cases with enhanced beta-catenin staining at the invasive margin and in tumor buds, respectively, also revealed stronger pontin expression. Analysis of pontin expression in 8 patients by Western blotting confirmed the histologic results. These data suggest that upregulation and nuclear localization of pontin together with beta-catenin may contribute to progression of colorectal carcinoma.
Lauscher
Johannes C
JC
Department of General, Vascular and Thoracic Surgery, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, D-12200 Berlin, Germany. Electronic address: johannes.lauscher@charite.de.
Loddenkemper
Christoph
C
Department of Pathology, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, D-12200 Berlin, Germany.
Kosel
Luise
L
Department of Laboratory Medicine and Pathobiochemistry, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, D-12200 Berlin, Germany.
Gröne
Jörn
J
Department of General, Vascular and Thoracic Surgery, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, D-12200 Berlin, Germany.
Buhr
Heinz J
HJ
Department of General, Vascular and Thoracic Surgery, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, D-12200 Berlin, Germany.
Huber
Otmar
O
Department of Laboratory Medicine and Pathobiochemistry, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, D-12200 Berlin, Germany. Electronic address: otmar.huber@charite.de.
D000074183:ATPases Associated with Diverse Cellular Activities; D000230:Adenocarcinoma / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D002352:Carrier Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C486549:RUVBL1 protein, human