ADAM28 is overexpressed in human non-small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis.
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 < or =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.
Ohtsuka
Takashi
T
Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
Shiomi
Takayuki
T
Shimoda
Masayuki
M
Kodama
Takahide
T
Amour
Augustin
A
Murphy
Gillian
G
Ohuchi
Eiko
E
Kobayashi
Koichi
K
Okada
Yasunori
Y
D051722:ADAM Proteins / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D051722:ADAM Proteins; C410224:ADAM28 protein, human