title: Effects of 5-aza-2'deoxycytidine on RECK gene expression and tumor invasion in salivary adenoid cystic carcinoma.
abstract: Reversion-inducing cysteine-rich protein with kazal motifs (RECK), a novel tumor suppressor gene that negatively regulates matrix metalloproteinases (MMPs), is expressed in various normal human tissues but downregulated in several types of human tumors. The molecular mechanism for this downregulation and its biological significance in salivary adenoid cystic carcinoma (SACC) are unclear. In the present study, we investigated the effects of a DNA methyltransferase (DNMT) inhibitor, 5-aza-2'deoxycytidine (5-aza-dC), on the methylation status of the RECK gene and tumor invasion in SACC cell lines. Methylation-specific PCR (MSP), Western blot analysis, and quantitative real-time PCR were used to investigate the methylation status of the RECK gene and expression of RECK mRNA and protein in SACC cell lines. The invasive ability of SACC cells was examined by the Transwell migration assay. Promoter methylation was only found in the ACC-M cell line. Treatment of ACC-M cells with 5-aza-dC partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression of mRNA and protein, and 5-aza-dC significantly suppressed ACC-M cell invasive ability. Our findings showed that 5-aza-dC inhibited cancer cell invasion through the reversal of RECK gene hypermethylation, which might be a promising chemotherapy approach in SACC treatment.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan, China.
authors.forename: X Q
authors.initials: XQ
authors.lastname: Zhou
authors.affiliation: Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan, China.
authors.forename: S Y
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan, China.
authors.forename: D S
authors.initials: DS
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan, China.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan, China.
authors.forename: W G
authors.initials: WG
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan, China.
authors.forename: Z W
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan, China.
authors.forename: H W
authors.initials: HW
authors.lastname: Wu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects; D058851:GPI-Linked Proteins / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D000964:Antimetabolites, Antineoplastic; D058851:GPI-Linked Proteins; C115460:RECK protein, human; D001374:Azacitidine