Role of myeloid cell leukemia-1 in cell growth of squamous cell carcinoma

Masahide Nagata, Koichiro Wada, Atsushi Nakajima, Noriko Nakajima, Morio Kusayama, Tomotake Masuda, Seiji Iida, Masaya Okura, Mikihiko Kogo, Yoshinori Kamisaki

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Myeloid cell leukemia-1 (Mcl-1), a member of the B-cell lymphoma-2 (Bcl-2) family, has been reported to be a critical survival factor in hematopoietic cells, yet little data exists for a role of Mcl-1 in human oral squamous cell carcinoma (SCC). A high level expression of Mcl-1 was observed in tumor cells of human primary SCC, lymph node metastasis tissues, and SCC cell lines. We manipulated expression of Mcl-1 protein in SCC cells by small interfering RNA (siRNA) for Mcl-1 and observed that Mcl-1 siRNA inhibited the growth of SCCs accompanied with apoptosis. Combination therapy of Mcl-1 siRNA and anti-tumor drug drastically inhibited the cell growth in comparison to that in each single treatment. In addition, phosphorylation of focal adhesion kinase (FAK) was decreased by treatment with Mcl-1 siRNA, resulting in decreases in phosphorylation of MEK1/2 and MAPK. The cell growth inhibition caused by knockdown of Mcl-1 was suggested to be mainly a result of suppression of proliferation via the inhibition of intracellular FAK/MAPK signaling pathways. These results imply a potentially important and novel role of the inhibition of Mcl-1 function by the use of specific siRNA in the treatment of SCC.

Original languageEnglish
Pages (from-to)344-353
Number of pages10
JournalJournal of Pharmacological Sciences
Volume110
Issue number3
DOIs
Publication statusPublished - Aug 3 2009
Externally publishedYes

Keywords

  • Apoptosis
  • Human
  • Myeloid cell leukemia-1 (Mcl-1)
  • Small interfering RNA (siRNA)
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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  • Cite this

    Nagata, M., Wada, K., Nakajima, A., Nakajima, N., Kusayama, M., Masuda, T., Iida, S., Okura, M., Kogo, M., & Kamisaki, Y. (2009). Role of myeloid cell leukemia-1 in cell growth of squamous cell carcinoma. Journal of Pharmacological Sciences, 110(3), 344-353. https://doi.org/10.1254/jphs.08339FP