ADAM28 is overexpressed in human non-small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis

Takashi Ohtsuka, Takayuki Shiomi, Masayuki Shimoda, Takahide Kodama, Augustin Amour, Gillian Murphy, Eiko Ohuchi, Koichi Kobayashi, Yasunori Okada

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)263-273
Number of pages11
JournalInternational Journal of Cancer
Volume118
Issue number2
DOIs
Publication statusPublished - 2006 Jan 15

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Non-Small Cell Lung Carcinoma
Lymph Nodes
Cell Proliferation
Neoplasm Metastasis
Metalloproteases
Carcinoma
Disintegrins
Snake Venoms
Consensus Sequence
Human Activities
In Situ Hybridization
Real-Time Polymerase Chain Reaction
Catalytic Domain
Immunohistochemistry
Polymerase Chain Reaction
Lung
Messenger RNA
Membranes
Proteins

Keywords

  • ADAM
  • Lung cancer
  • Metastasis
  • MMP
  • Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

ADAM28 is overexpressed in human non-small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis. / Ohtsuka, Takashi; Shiomi, Takayuki; Shimoda, Masayuki; Kodama, Takahide; Amour, Augustin; Murphy, Gillian; Ohuchi, Eiko; Kobayashi, Koichi; Okada, Yasunori.

In: International Journal of Cancer, Vol. 118, No. 2, 15.01.2006, p. 263-273.

Research output: Contribution to journalArticle

Ohtsuka, Takashi ; Shiomi, Takayuki ; Shimoda, Masayuki ; Kodama, Takahide ; Amour, Augustin ; Murphy, Gillian ; Ohuchi, Eiko ; Kobayashi, Koichi ; Okada, Yasunori. / ADAM28 is overexpressed in human non-small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis. In: International Journal of Cancer. 2006 ; Vol. 118, No. 2. pp. 263-273.
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AU - Ohtsuka, Takashi

AU - Shiomi, Takayuki

AU - Shimoda, Masayuki

AU - Kodama, Takahide

AU - Amour, Augustin

AU - Murphy, Gillian

AU - Ohuchi, Eiko

AU - Kobayashi, Koichi

AU - Okada, Yasunori

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N2 - 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.

AB - 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.

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