title: Expression and role of HMGA1 in renal cell carcinoma.
abstract: OBJECTIVE
  Although molecular targeted therapy has improved the clinical outcome of metastatic renal cell carcinoma, a complete response is rare and there are various side effects. Identifying novel target molecules is necessary to improve the clinical outcome of metastatic renal cell carcinoma. HMGA1 is over expressed in many types of cancer and it is associated with metastatic potential. It is expressed at low levels or not expressed in normal tissue. We examined HMGA1 expression and function in human renal cell carcinoma.
  
  
  METHODS
  HMGA1 expression in surgical specimen from patients with renal cell carcinoma was examined by immunoblot. HMGA1 expression in 6 human renal cell carcinoma cell lines was examined by immunoblot and immunofluorescence. The molecular effects of siRNA mediated knockdown of HMGA1 were examined in ACHN and Caki-1 cells.
  
  
  RESULTS
  Immunoblot using surgical specimen showed that HMGA1 was not expressed in normal kidney tissue but it was expressed in tumor tissue in 1 of 30 nonmetastatic (3%) and 6 of 18 metastatic (33%) cases (p=0.008). Immunoblot and immunofluorescence revealed significant nuclear expression of HMGA1 in ACHN and Caki-1 cells derived from metastatic sites. HMGA1 knockdown remarkably suppressed colony formation and induced significant apoptosis in ACHN and Caki-1 cells. HMGA1 knockdown significantly inhibited invasion and migration in vitro, and induced anoikis associated with P-Akt down-regulation in ACHN cells.
  
  
  CONCLUSIONS
  HMGA1 is a potential target for novel therapeutic modalities for metastatic renal cell carcinoma.
authors.affiliation: Department of Translational Cancer Drug Development, Kyoto Prefectural University of Medicine, Kyoto, Japan. ntakaha@koto.kpu-m.ac.jp
authors.forename: Natsuki
authors.initials: N
authors.lastname: Takaha
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sowa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takeuchi
authors.forename: Fumiya
authors.initials: F
authors.lastname: Hongo
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kawauchi
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Miki
mesh_terms: D023102:Anoikis / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D025741:HMGA1a Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D025741:HMGA1a Protein