Galanin has tumor suppressor activity and is frequently inactivated by aberrant promoter methylation in head and neck cancer.

Abstract

PURPOSE:

There is accumulating evidence that galanin 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 primary tumors, based on the hypothesis that CpG hypermethylation might silence the galanin gene.

EXPERIMENTAL DESIGN:

Galanin expression was examined using reverse transcription-polymerase chain reaction (PCR). The methylation status of the galanin promoter was studied using bisulfate sequencing and methylation-specific PCR. UM-SCC-54 was stably transfected to express galanin.

RESULTS:

Galanin expression was absent in 3/12 (25.0%) UM-SCC cell lines, whereas three nonmalignant cell lines had stable expression. Galanin methylation was found in 24/100 (24.0%) cases. HNSCC tumor specimens was significantly correlated with the GALR1 methylation status (P = 1.88E-06). The presence of galanin promoter hypermethylation was statistically correlated with a decrease in disease-free survival (log-rank test, P = 6.02E-05). A multivariate logistic regression analysis showed that methylation of galanin and methylation of the gene pair galanin and GALR1 had an odds ratio for recurrence of 8.95 [95% confidence interval (CI), 2.29-35.03] and 23.84 (95% CI, 2.74-207.17), respectively. UM-SCC-54 cells that are GALR1-proficient but have hypermethylated galanin exhibited suppressed cell proliferation following exogenous expression of galanin.

CONCLUSIONS:

Association of frequent promoter hypermethylation and gene silencing with poor survival, combined with growth suppression of HNSCC cells after forced gene expression, supports the hypothesis that galanin acts as a tumor suppressor. These data suggest that galanin and GALR1 are potential therapeutic targets and prognostic factors.

• Authors: Kiyoshi Misawa, Takeharu Kanazawa, Yuki Misawa, Takayuki Uehara, Atsushi Imai, Goro Takahashi, Satoru Takebayashi, Andrew Cole, Thomas E Carey, Hiroyuki Mineta
• Journal: Translational oncology (Transl Oncol) Vol. 6 Issue 3 Pg. 338-46 (Jun 2013) ISSN: 1936-5233 [Print] United States
• PMID: 23730414 (Publication Type: Journal Article)