title: The role of MAGEA2 in head and neck cancer.
abstract: OBJECTIVE
  To examine the role of MAGEA2 in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Primary tissue microarray data and quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed that MAGEA2 is differentially overexpressed in HNSCC. Functional analyses were then performed using MAGEA2 transfections and small-interfering RNA knockdowns with subsequent anchorage-dependent growth studies and cell cycle analyses. Quantitative RT-PCR was used to evaluate expression changes in p53 downstream targets after transfection of MAGEA2 into normal upper aerodigestive cell lines.
  
  
  RESULTS
  MAGEA2 is differentially overexpressed in HNSCC. In addition, MAGEA2 promotes growth in normal oral keratinocytes, whereas knockdown of MAGEA2 in HNSCC cells decreases growth. Using the HCT116 p53 wt and null cell line system, transfection of MAGEA2 induced growth in the p53 wt cell line while providing no growth advantage in the p53 mutant cells. Subsequently, transfection of MAGEA2 induced a decrease in messenger RNA expression of the p53 downstream targets CDKN1A and BAX and decreased G1 arrest in cells allowed to remain confluent for longer than 48 hours.
  
  
  CONCLUSIONS
  These data suggest that MAGEA2 is differentially expressed in HNSCC and functions, in part, through the p53 pathway by increasing cellular proliferation and abrogating cell cycle arrest. This improved understanding of MAGEA2 function and expression patterns will potentially allow for the improved ability to use MAGEA2 for detection, surveillance, and targeted therapeutics.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Medical Institutions, 1550 Orleans St, Room 5N.04, Baltimore, MD 21231, USA.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Glazer
authors.forename: Ian M
authors.initials: IM
authors.lastname: Smith
authors.forename: Sheetal
authors.initials: S
authors.lastname: Bhan
authors.forename: Wenyue
authors.initials: W
authors.lastname: Sun
authors.forename: Steven S
authors.initials: SS
authors.lastname: Chang
authors.forename: Kavita M
authors.initials: KM
authors.lastname: Pattani
authors.forename: William
authors.initials: W
authors.lastname: Westra
authors.forename: Zubair
authors.initials: Z
authors.lastname: Khan
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000473:pathology; D051379:Mice; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010039:Otorhinolaryngologic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; C420909:Mage-a2 antigen; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53