title: Identification of TRPC6 as a possible candidate target gene within an amplicon at 11q21-q22.2 for migratory capacity in head and neck squamous cell carcinomas.
abstract: BACKGROUND
  Cytogenetic and gene expression analyses in head and neck squamous cell carcinomas (HNSCC) have allowed identification of genomic aberrations that may contribute to cancer pathophysiology. Nevertheless, the molecular consequences of numerous genetic alterations still remain unclear.
  
  
  METHODS
  To identify novel genes implicated in HNSCC pathogenesis, we analyzed the genomic alterations present in five HNSCC-derived cell lines by array CGH, and compared high level focal gene amplifications with gene expression levels to identify genes whose expression is directly impacted by these genetic events. Next, we knocked down TRPC6, one of the most highly amplified and over-expressed genes, to characterize the biological roles of TRPC6 in carcinogenesis. Finally, real time PCR was performed to determine TRPC6 gene dosage and mRNA levels in normal mucosa and human HNSCC tissues.
  
  
  RESULTS
  The data showed that the HNSCC-derived cell lines carry most of the recurrent genomic abnormalities previously described in primary tumors. High-level genomic amplifications were found at four chromosomal sites (11q21-q22.2, 18p11.31-p11.21, 19p13.2-p13.13, and 21q11) with associated gene expression changes in selective candidate genes suggesting that they may play an important role in the malignant behavior of HNSCC. One of the most dramatic alterations of gene transcription involved the TRPC6 gene (located at 11q21-q22.2) which has been recently implicated in tumour invasiveness. siRNA-induced knockdown of TRPC6 expression in HNSCC-derived cells dramatically inhibited HNSCC-cell invasion but did not significantly alter cell proliferation. Importantly, amplification and concomitant overexpression of TRPC6 was also found in HNSCC tumour samples.
  
  
  CONCLUSIONS
  Altogether, these data show that TRPC6 is likely to be a target for 11q21-22.2 amplification that confers enhanced invasive behavior to HNSCC cells. Therefore, TRPC6 may be a promising therapeutic target in the treatment of HNSCC.
authors.affiliation: Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Bernaldo de Quirós
authors.forename: Anna
authors.initials: A
authors.lastname: Merlo
authors.forename: Pablo
authors.initials: P
authors.lastname: Secades
authors.forename: Iriana
authors.initials: I
authors.lastname: Zambrano
authors.forename: Ines Saenz
authors.initials: IS
authors.lastname: de Santa María
authors.forename: Nerea
authors.initials: N
authors.lastname: Ugidos
authors.forename: Eloisa
authors.initials: E
authors.lastname: Jantus-Lewintre
authors.forename: Rafael
authors.initials: R
authors.lastname: Sirera
authors.forename: Carlos
authors.initials: C
authors.lastname: Suarez
authors.forename: María-Dolores
authors.initials: MD
authors.lastname: Chiara
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D050052:TRPC Cation Channels / Q000235:genetics* / Q000378:metabolism; D000074287:TRPC6 Cation Channel
chemical_list: D014408:Biomarkers, Tumor; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human