Expression of SIP1 in oral squamous cell carcinomas: implications for E-cadherin expression and tumor progression.
Loss of E-cadherin expression allows carcinoma cells to liberate from the primary site and enhances invasion and metastasis. The genetic aberration of E-cadherin is a rare event in sporadic carcinomas, and transcription repressors are considered to take a central role in E-cadherin loss. However, expression of E-cadherin repressors is largely dependent on tissue and cell type. To identify the repressor expressed in oral squamous carcinomas, we compared the expression levels of E-cadherin and repressors by real-time RT-PCR. Among the repressors including SNAIL, SLUG, SIP1, E12 and E47, SIP1 was inversely correlated to E-cadherin (P < 0.05). Chromatin immunoprecipitation showed that SIP1 specifically bound to the E-cadherin promoter region. SIP1 expression was immuno-histochemically detected in 27.7% of 47 oral carcinomas, and SIP1-positive carcinomas did not express E-cadherin (P < 0.01). Thirteen patients with SIP1 staining showed a lower disease-specific survival rate (P < 0.05). Multivariate risk factor analysis demonstrated that SIP1 expression was an independent prognostic value for disease-specific overall survival (P < 0.05). These results suggest that SIP1 contributes to the loss of E-cadherin expression and that detection of SIP1 expression is a predictive and prognostic tool in clinical management of oral carcinomas.
Maeda
Genta
G
Department of Biochemistry, School of Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
Chiba
Tadashige
T
Okazaki
Masahiro
M
Satoh
Tazuko
T
Taya
Yuji
Y
Aoba
Takaaki
T
Kato
Koroku
K
Kawashiri
Shuichi
S
Imai
Kazushi
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001665:Binding Sites / Q000235:genetics; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D000074165:Zinc Finger E-box Binding Homeobox 2
D015820:Cadherins; D018398:Homeodomain Proteins; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2