Tumor suppressor activity and inactivation of galanin receptor type 2 by aberrant promoter methylation in head and neck cancer. Issue 2 (10th October 2013)

• Record Type: Journal Article
• Authors: Misawa, Yuki; Misawa, Kiyoshi; Kanazawa, Takeharu; Uehara, Takayuki; Endo, Shori; Mochizuki, Daiki; Yamatodani, Takashi; Carey, Thomas E.; Mineta, Hiroyuki
• Is Part Of: Cancer. Volume 120:Issue 2(2014)
• Page Start: 205
• Page End: 213
• Publication Date: 2013-10-10
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28411
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28411-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>There is accumulating evidence that <italic>galanin</italic> receptors (GALRs) may be tumor suppressors in head and neck squamous cell carcinoma (HNSCC). Promoter methylation status and gene expression were assessed in a large panel of head and neck primary tumors, based on the hypothesis that cytosine‐guanine dinucleotide (CpG) hypermethylation might silence the <italic>galanin</italic> receptor 2 (<italic>GALR2</italic>) gene.</p> </sec> <sec id="cncr28411-sec-0002" sec-type="section"> <title>METHODS</title> <p> <italic>GALR2</italic> expression was examined in a panel of cell lines by using quantitative reverse transcription polymerase chain reaction (RT‐PCR). The methylation status of the <italic>GALR2</italic> promoter was studied using quantitative methylation‐specific PCR (Q‐MSP). UM‐SCC‐1 was stably transfected to express <italic>GALR2</italic>.</p> </sec> <sec id="cncr28411-sec-0003" sec-type="section"> <title>RESULTS</title> <p> <italic>GALR2</italic> expression was suppressed in UM‐SCC cell lines, whereas nonmalignant cell lines exhibited stable expression. <italic>GALR2</italic> methylation found in 31 of 100 (31.0%) tumor specimens was significantly correlated with the methylation status of both <italic>GALR1</italic> and <italic>Galanin</italic>. The observed <italic>GALR2</italic> promoter hypermethylation was statistically correlated with a decrease in disease‐free survival (log‐rank test, <italic>P</italic> = .045). A multivariate logistic‐regression analysis revealed a high odds ratio for recurring methylation of <italic>GALR2</italic> and the gene pair <italic>GALR2</italic> and <italic>Galanin</italic>, 8.95 (95% confidence interval, 2.29‐35.03; <italic>P</italic> = .024) and 9.05 (95% confidence interval, 1.76‐46.50; <italic>P</italic> = .008), respectively. In addition, exogenous expression of <italic>GALR2</italic> suppressed cell proliferation in UM‐SCC‐1 cells with hypermethylated <italic>Galanin</italic> and <italic>GALR2</italic>‐proficient cell lines.</p> </sec> <sec id="cncr28411-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>Frequent promoter hypermethylation in association with prognosis, and growth suppression after re‐expression, supports the hypothesis that <italic>GALR2</italic> may act to suppress tumor activity. <italic>GALR2</italic> is a potentially significant therapeutic target and prognostic factor for this cancer type. <bold><italic>Cancer</italic> 2014;120:205–213</bold>. © <italic>2013 American Cancer Society</italic>.</p> </sec> </abstract>