Midkine expression is correlated with an adverse prognosis and is down-regulated by p53 in oral squamous cell carcinoma.
Midkine (MK) expression has been documented to be inversely correlated with the prognosis of patients with various tumors, but the mechanism of this relationship has not been well characterized. Recent studies have also correlated p53 expression with prognosis of patients with oral squamous cell carcinoma (OSCC). We evaluated the relationship between MK expression and clinicopathological features of patients with OSCC to clarify the influence of p53 status on MK expression in OSCC cells. Our results showed that patients with MK over-expression in OSCC cells had a significantly lower 5-year survival rate compared with patients with low MK expression. Immunohistochemical analyses demonstrated overexpression of MK protein in OSCC samples with mutant p53. Cell culture experiments with human lingual squamous cell carcinoma revealed that the MK gene was regulated by the wild-type p53 gene. Thus, MK expression may affect prognosis via the p53 status and mutation of the p53 gene, and MK may be an attractive target for therapeutic intervention in patients with cancer cells with mutant p53.
Ota
Kazutoshi
K
Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Fujimori
Hiromi
H
Ueda
Mitsuharu
M
Jono
Hirofumi
H
Shinriki
Satoru
S
Ota
Tomoko
T
Sueyoshi
Takanao
T
Taura
Manabu
M
Taguma
Ayaka
A
Kai
Hirofumi
H
Shinohara
Masanori
M
Ando
Yukio
Y
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000078792:Midkine; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D016207:Cytokines; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000078792:Midkine