title: Coexpression of hypoxia-inducible factor-2α, TWIST2, and SIP1 may correlate with invasion and metastasis of salivary adenoid cystic carcinoma.
abstract: BACKGROUND
  Adenoid cystic carcinoma (ACC) of salivary gland is characterized by advanced local invasion and distant metastasis. Intratumoral hypoxia was reported to be associated with epithelial-mesenchymal transition (EMT) regulators. The purpose of this study was to evaluate the relationship between hypoxia-inducible factor (HIF)-2α, TWIST2, and SIP1 expression and the invasion and metastasis in ACC of salivary gland.
  
  
  METHODS
  In vitro we first detected the expression of HIF-2α, TWIST2, and SIP1 in two ACC cell lines by Western blot and real-time RT-PCR. Then, in vivo, a retrospective investigation of 121 patients with ACC from Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University between 1996 and 2005 was carried out using immunohistochemistry to analyze the association between the expression of these three factors and clinical-pathological factors of patients.
  
  
  RESULTS
  The protein and mRNA levels of HIF-2α, TWIST2, and SIP1 in the high-metastasis cell line (ACC-M) were much higher than those of the low-metastasis cell line (ACC-2). The positive expression of HIF-2α, TWIST2, and SIP1 (71.07%, 42.98%, and 38.02%, respectively) was associated with the perineural invasion, the local recurrence, and distant metastasis of patients with ACC (P < 0.05). The patients with the positive coexpression of the three factors had a lower survival rate than those with the negative expression (P < 0.05).
  
  
  CONCLUSIONS
  It is proposed that the elevated expression of HIF-2α, TWIST2, and SIP1 can contribute to invasion and metastasis of ACC, and there might be some correlation between the hypoxia microenvironment and EMT in ACC.
authors: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, Sichuan, China.
authors: Chenchen
authors: C
authors: Zhou
authors: Jeffrey
authors: J
authors: Liu
authors: Yaling
authors: Y
authors: Tang
authors: Guiquan
authors: G
authors: Zhu
authors: Min
authors: M
authors: Zheng
authors: Jian
authors: J
authors: Jiang
authors: Jing
authors: J
authors: Yang
authors: Xinhua
authors: X
authors: Liang
mesh_terms: D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D051879:Twist-Related Protein 1; D000099162:Endothelial PAS Domain-Containing Protein 1; C108381:GEMIN2 protein, human; C486274:TWIST2 protein, human