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Cancer Biology |
B Activation
Departments of 1 Cancer Therapy and Research, 2 Anatomic Pathology, and 3 Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Purpose: We examined the role of interleukin (IL)-1ß in activation of nuclear factor
B (NF-
B) and the biological function of activated NF-
B in gastric carcinoma cells.
Experimental Design: Human gastric carcinoma cell line GCTM-1 was used to examine NF-
B activation by immunostaining and electrophoretic mobility shift assay. Matrix metalloproteinase (MMP)-9 expression, which plays an important role in tumor invasion, was assessed by semiquantitative reverse transcription-PCR, Western blotting, and immunostaining. The invasive ability of GCTM-1 cells was measured by Matrigel invasion assay. In vivo expression of IL-1ß and MMP-9 and activation of NF-
B in 10 surgically resected gastric carcinoma specimens were examined immunohistochemically.
Results: IL-1ß enhanced NF-
B activation, MMP-9 expression, and the invasive ability of GCTM-1. A NF-
B inhibitor, pyrrolidine dithiocarbamate, suppressed both MMP-9 expression and invasiveness of IL-1ß-treated GCTM-1 cells. IL-1ß did not increase the invasive ability of GCTM-1 cells transfected with MMP-9 antisense oligonucleotide. Concomitant expression of IL-1ß and nuclear NF-
B was observed in 3 of 10 gastric carcinoma specimens. Cells producing IL-1ß were tumor-infiltrating macrophages in two specimens and gastric carcinoma cells in one specimen.
Conclusions: One of the molecules that may play a role in NF-
B activation in some gastric carcinomas is IL-1ß. The present results suggest that IL-1ß increases the invasive ability of carcinoma cells through activation of NF-
B and the resulting MMP-9 expression.
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