TY - JOUR
T1 - ADAMTSL3/punctin-2, a gene frequently mutated in colorectal tumors, is widely expressed in normal and malignant epithelial cells, vascular endothelial cells and other cell types, and its mRNA is reduced in colon cancer
AU - Koo, Bon Hun
AU - Hurskainen, Tiina
AU - Mielke, Katrina
AU - Phyu, Phyu Aung
AU - Casey, Graham
AU - Autio-Harmainen, Helena
AU - Apte, Suneel S.
N1 - Funding Information:
The authors are grateful to the staff, nurses and doctors of the hospitals for their care of the patients. We are also grateful to the field and laboratory staff of the project; Olajumoke Imolehin, Funmilola Ajayi, Folakemi Amodu and Mojisola Oyeniyi. The research leading to these results has received funding from the European Community under grant agreement LSHP-CT-2004-503578 and Seventh Framework Programme (FP7/2007-2013) under grant agreement N° 242095.
Funding Information:
The authors are grateful to the staff, nurses and doctors of the hospitals for their care of the patients. We are also grateful to the field and laboratory staff of the project; Olajumoke Imolehin, Funmilola Ajayi, Folakemi Amodu and Mojisola Oyeniyi. The research leading to these results has received funding from the European Community under grant agreement LSHP-CT-2004-503578 and Seventh Framework Programme (FP7/2007-2013) under grant agreement N° 242095
PY - 2007/10/15
Y1 - 2007/10/15
N2 - ADAMTSL3/punctin-2 is a secreted glycoprotein that resembles the ADAMTS proteases. Recently, identification of frequent ADAMTSL3 mutations in colorectal cancer suggested it might have a regulatory role in cellular homeostasis in colorectal epithelium or in pathways to colorectal malignancy. Here, we used in situ hybridization to validate ADAMTSL3 antibodies for IHC of a variety of normal and malignant tissues, including colon cancer. Quantitative real-time PCR (RTQ-PCR) was used to compare mRNA expression levels in colon carcinoma (n = 10) and adjacent normal colon. ADAMTSL3 is expressed in epithelial cells of the colon, fallopian tube, skin, breast, prostate, epididymis, liver, pancreatic islets and bile ducts, as well as by vascular endothelial cells, smooth muscle cells, fibroblasts, cortical and ganglionic neurons and cardiac myocytes. Malignant epithelial cells in colon cancer, as well as breast, prostate, renal and skin tumors expressed ADAMTSL3. Normal colon showed stronger immunostaining of surface than basal crypt epithelium and staining of a variety of cells within the lamina propria and submucosa. Colon carcinomas demonstrated weaker staining in tumor cells than normal colon epithelium and weak stromal staining. RTQ-PCR comparison of ADAMTSL3 mRNA in colon carcinoma and adjacent normal colon demonstrated a statistically significant reduction in the tumors, possibly reflecting their decreased stromal content and lack of complete differentiation of tumor samples. The major findings of these studies are that ADAMTSL3 is expressed in numerous tissues, suggesting a broader regulatory role than in colorectal epithelium alone, and that colorectal cancer has both structural mutations as well as decreased expression of ADAMTSL3.
AB - ADAMTSL3/punctin-2 is a secreted glycoprotein that resembles the ADAMTS proteases. Recently, identification of frequent ADAMTSL3 mutations in colorectal cancer suggested it might have a regulatory role in cellular homeostasis in colorectal epithelium or in pathways to colorectal malignancy. Here, we used in situ hybridization to validate ADAMTSL3 antibodies for IHC of a variety of normal and malignant tissues, including colon cancer. Quantitative real-time PCR (RTQ-PCR) was used to compare mRNA expression levels in colon carcinoma (n = 10) and adjacent normal colon. ADAMTSL3 is expressed in epithelial cells of the colon, fallopian tube, skin, breast, prostate, epididymis, liver, pancreatic islets and bile ducts, as well as by vascular endothelial cells, smooth muscle cells, fibroblasts, cortical and ganglionic neurons and cardiac myocytes. Malignant epithelial cells in colon cancer, as well as breast, prostate, renal and skin tumors expressed ADAMTSL3. Normal colon showed stronger immunostaining of surface than basal crypt epithelium and staining of a variety of cells within the lamina propria and submucosa. Colon carcinomas demonstrated weaker staining in tumor cells than normal colon epithelium and weak stromal staining. RTQ-PCR comparison of ADAMTSL3 mRNA in colon carcinoma and adjacent normal colon demonstrated a statistically significant reduction in the tumors, possibly reflecting their decreased stromal content and lack of complete differentiation of tumor samples. The major findings of these studies are that ADAMTSL3 is expressed in numerous tissues, suggesting a broader regulatory role than in colorectal epithelium alone, and that colorectal cancer has both structural mutations as well as decreased expression of ADAMTSL3.
KW - ADAMTS
KW - ADAMTSL3
KW - Colorectal cancer
KW - Glycoprotein
KW - Punctin
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U2 - 10.1002/ijc.22882
DO - 10.1002/ijc.22882
M3 - Article
C2 - 17597111
AN - SCOPUS:34548682054
SN - 0020-7136
VL - 121
SP - 1710
EP - 1716
JO - International journal of cancer
JF - International journal of cancer
IS - 8
ER -