Demethylation treatment restores hic1 expression and impairs aggressiveness of head and neck squamous cell carcinoma.
Promoter hypermethylation of tumor suppressor genes is a common feature of primary cancer cells. However, at date the somatic epigenetic events that occur in head and neck squamous cell carcinoma (HNSCC) tumorigenesis are not yet been well defined. In the present study we analysed the methylation status of the gene hypermethylated in cancer-1 (hic1), a gene located on chromosome 17p13.3, a region frequently lost in HNSCC. We analysed 22 HNSCC samples and three cell lines using methylation specific PCR (MSP). We found hic1 methylated in 21 out of 22 samples and in all three cell lines. Treatment of the cell lines with the demethylating agent 5-Azacytidin (5-Aza) resulted in the demethylation of the hic1 promoter and reactivation of hic1 expression as determined by MSP, qPCR and Western blot. Functional analyses revealed decreased proliferative activity and colony forming ability of treated cells. In summary, we found in HNSCC hic1 regulated by promoter methylation. 5-Aza application resulted in the reexpression of hic1 and was followed by decreased aggressiveness of the cancer cells. Our data indicate that hic1 might be a player in HNSCC development and suggest further evaluation of 5-Aza for HNSCC treatment.
Brieger
Juergen
J
Department of Otolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. brieger@mail.uni-mainz.de
Pongsapich
Warut
W
Mann
Sylvia A
SA
Hedrich
Jana
J
Fruth
Kai
K
Pogozelski
Benjamin
B
Mann
Wolf J
WJ
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001374:Azacitidine / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic
D000964:Antimetabolites, Antineoplastic; C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; D001374:Azacitidine