Role of myeloid cell leukemia-1 in cell growth of squamous cell carcinoma.
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.
Nagata
Masahide
M
Department of Pharmacology, Graduate School of Dentistry, Osaka University, Japan.
Wada
Koichiro
K
Nakajima
Atsushi
A
Nakajima
Noriko
N
Kusayama
Morio
M
Masuda
Tomotake
T
Iida
Seiji
S
Okura
Masaya
M
Kogo
Mikihiko
M
Kamisaki
Yoshinori
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000627:therapeutic use; D014062:Tongue Neoplasms / Q000188:drug therapy / Q000473:pathology*
D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human