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ADAM28 is overexpressed in human non‐small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis
Author(s) -
Ohtsuka Takashi,
Shiomi Takayuki,
Shimoda Masayuki,
Kodama Takahide,
Amour Augustin,
Murphy Gillian,
Ohuchi Eiko,
Kobayashi Koichi,
Okada Yasunori
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21324
Subject(s) - biology , metastasis , carcinoma , metalloproteinase , pathology , immunohistochemistry , disintegrin , lymph node , in situ hybridization , cancer research , cell , cell culture , microbiology and biotechnology , gene expression , cancer , matrix metalloproteinase , gene , medicine , immunology , genetics , biochemistry
ADAM (a disintegrin and metalloproteinases) are a recently discovered gene family of proteins with sequence similarity to the reprolysin family of snake venom metalloproteinases, and about one‐third of the family members have the catalytic site consensus sequence in their metalloproteinase domains. We screened the mRNA expression of 11 different ADAM species with putative metalloproteinase activity in human non‐small cell lung carcinomas by RT‐PCR, and found that prototype membrane‐anchored ADAM28 (ADAM28m) and secreted ADAM28 (ADAM28s) are predominantly expressed in the carcinoma tissues. Real‐time quantitative PCR demonstrated that the expression levels of ADAM28m and ADAM28s are significantly 16.8‐fold and 9.0‐fold higher in the carcinomas than in the non‐carcinoma tissues, respectively. In addition, the expression levels of ADAM28m and ADAM28s were significantly higher in the carcinomas with >30 mm in diameter than in those ≦30 mm. The expression levels were also significantly higher in the carcinomas with lymph node metastasis than in those without metastasis. MIB1‐positive cell index of the carcinomas had a direct correlation with the expression levels of ADAM28m and ADAM28s ( r = 0.667, p < 0.001 and r = 0.535, p < 0.01, respectively). In situ hybridization and immunohistochemistry demonstrated that ADAM28 is expressed predominantly in the carcinoma cells. Immunoblot analysis showed the activated form of ADAM28 in the carcinoma tissues. These data demonstrate for the first time that ADAM28 is overexpressed and activated in human non‐small cell lung carcinomas, and suggest the possibility that ADAM28 plays a role in cell proliferation and progression of the human lung carcinomas. © 2005 Wiley‐Liss, Inc.