Tumor necrosis factor-related apoptosis-inducing ligand induces apoptotic cell death through c-Jun NH2-terminal kinase activation in squamous cell carcinoma cells

  • Authors:
    • Takenori Noutomi
    • Mizue Itoh
    • Hiroko Toyota
    • Eiko Takada
    • Junichiro Mizuguchi
  • View Affiliations

  • Published online on: November 1, 2009     https://doi.org/10.3892/or_00000551
  • Pages: 1169-1172
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in MIT6 cells derived from primary oral squamous cell carcinoma (OSCC), whereas it does not induce apoptosis in MIL6 cells derived from metastases. The present studies were performed to examine whether activation of c-Jun NH2-terminal kinase (JNK) is implicated in the differential sensitivity to TRAIL-induced apoptosis. The TRAIL-induced JNK activation in MIT6 cells was stronger than in MIL6 cells, as assessed by Western blotting using antibodies specific for phospho-JNK. To evaluate the role of JNK1 in TRAIL-induced cell death, one clone expressing the dominant-negative form of JNK1 (dnJNK1) was established. The dnJNK1-expressing cells and MIL6 cells expressed TRAIL protein at levels similar to or even greater than MIT6 cells did. When cell death was assessed by annexin V staining and mitochondrial membrane potential, kinetic studies demonstrated that the dnJNK1-expressing cells were substantially more resistant to 100 ng/ml TRAIL, comparable to MIL6 cells, at 36 and 48 h after stimulation. Collectively, the primary OSCC cell line, MIT6, is sensitive to TRAIL but its metastatic line MIL6 is resistant to TRAIL exposure. Thus, the underlying molecular mechanism of TRAIL-induced cell death involves JNK activation. These results suggest that the acquisition of TRAIL resistance provides some metastatic capacity to primary tumors.

Related Articles

Journal Cover

November 2009
Volume 22 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Noutomi T, Itoh M, Toyota H, Takada E and Mizuguchi J: Tumor necrosis factor-related apoptosis-inducing ligand induces apoptotic cell death through c-Jun NH2-terminal kinase activation in squamous cell carcinoma cells. Oncol Rep 22: 1169-1172, 2009.
APA
Noutomi, T., Itoh, M., Toyota, H., Takada, E., & Mizuguchi, J. (2009). Tumor necrosis factor-related apoptosis-inducing ligand induces apoptotic cell death through c-Jun NH2-terminal kinase activation in squamous cell carcinoma cells. Oncology Reports, 22, 1169-1172. https://doi.org/10.3892/or_00000551
MLA
Noutomi, T., Itoh, M., Toyota, H., Takada, E., Mizuguchi, J."Tumor necrosis factor-related apoptosis-inducing ligand induces apoptotic cell death through c-Jun NH2-terminal kinase activation in squamous cell carcinoma cells". Oncology Reports 22.5 (2009): 1169-1172.
Chicago
Noutomi, T., Itoh, M., Toyota, H., Takada, E., Mizuguchi, J."Tumor necrosis factor-related apoptosis-inducing ligand induces apoptotic cell death through c-Jun NH2-terminal kinase activation in squamous cell carcinoma cells". Oncology Reports 22, no. 5 (2009): 1169-1172. https://doi.org/10.3892/or_00000551