Midkine induced growth of ameloblastoma through MAPK and Akt pathways.
Midkine (MK) is expressed during tooth development and, since ameloblastoma is thought to be arisen from the epithelium of the odontogenic apparatus or its remnant tissues, the effect of MK in ameloblastoma cell growth should be examined. The expression and function of MK were examined using 37 ameloblastoma tissues and AM-1 cells, an HPV-16DNA transfected ameloblastoma cell line. We found that MK was immunohistochemically expressed in 70% of ameloblastoma cases and AM-1 cells. By stimulation with 100 ng/ml MK, the growth of AM-1 cells was accelerated two fold by the 9th day. MK could induce phosphorylation of p44/42 MAPK (Thr202/Tyr204) and Akt (Ser473 and Thr308), and by pretreatment of PD98059, MEK1 inhibitor, or LY294002, PI3K inhibitor, MK-stimulated-phosphorylation of MAPK and Akt and MK-stimulated growth of AM-1 cells were inhibited. These results suggested that MK induced growth of ameloblastoma is through the MAPK and Akt pathways.
Sandra
F
F
Laboratory of Oral Cellular and Molecular Biology, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. ferry@dent.kyushu-u.ac.jp
Harada
H
H
Nakamura
N
N
Ohishi
M
M
D000564:Ameloblastoma / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000494:pharmacology* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007573:Jaw Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D000078792:Midkine; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D016207:Cytokines; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D000078792:Midkine; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases