Document Detail

Galanin receptor subtype 2 suppresses cell proliferation and induces apoptosis in p53 mutant head and neck cancer cells.
MedLine Citation:
PMID:  19276245     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Galanin and its three receptors (GALR1-3) are expressed in many normal tissues, but silenced in some tumors. Contradictory roles for galanin and its receptors in various tumors have been reported. To understand their function, investigations of individual galanin receptors are necessary. In head and neck squamous carcinoma cells (HNSCC) with silenced GALR1 and GALR2, we showed that reexpressed GALR1 suppresses tumor cell proliferation via Erk1/2-mediated effects on cdk inhibitors and cyclin D1. Others showed that GALR2 could induce apoptosis in neuroblastoma cells with wild-type p53, whereas GALR2 stimulated proliferation in small cell lung cancer. In this study, we investigated the role of GALR2 in HNSCC cells that have mutant p53 and do not express GALR1.
EXPERIMENTAL DESIGN: UM-SCC-1, a human oral carcinoma cell line with a splice site mutation causing a 46-bp p53 off-frame deletion, was stably transfected to express GALR2 (UM-SCC-1-GALR2).
RESULTS: Galanin treatment of UM-SCC-1-GALR2 caused morphologic changes and a marked decrease in cell number that were not observed in UM-SCC-1-mock cells. Galanin and GALR2 resulted in decreased bromodeoxyuridine incorporation, p27(Kip1) and p57(Kip2) up-regulation, and decreased cyclin D1 expression. These effects were similar to GALR1 signaling in HNSCC, but GALR2 also induced caspase-3-dependent apoptosis, which was confirmed by Annexin-V staining and DNA fragmentation analysis. These were not observed with GALR1.
CONCLUSION: This study shows that GALR2 reexpression can inhibit cell proliferation and induce apoptosis in HNSCC cells with mutant p53. GALR2 may be a feasible target for HNSCC therapy.
Takeharu Kanazawa; Pavan K Kommareddi; Toshihide Iwashita; Bhavna Kumar; Kiyoshi Misawa; Yuki Misawa; Ilwhan Jang; Thankam S Nair; Yukiko Iino; Thomas E Carey
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-03-10
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  15     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-02     Completed Date:  2009-10-22     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2222-30     Citation Subset:  IM    
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MeSH Terms
Carcinoma, Squamous Cell / genetics,  metabolism*,  pathology
Caspase 3 / metabolism
Cell Adhesion
Cell Line, Tumor
Cell Proliferation
Cyclin D1 / metabolism
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Cyclin-Dependent Kinase Inhibitor p57 / metabolism
Genes, p53*
Head and Neck Neoplasms / genetics,  metabolism*,  pathology
Receptor, Galanin, Type 2 / metabolism*
Grant Support
1P50 CA97248/CA/NCI NIH HHS; 5P30 CA46592/CA/NCI NIH HHS; P30 CA046592/CA/NCI NIH HHS; P30 CA046592-20/CA/NCI NIH HHS; P30 DC005188/DC/NIDCD NIH HHS; P30 DC005188-06/DC/NIDCD NIH HHS; P50 CA097248-07/CA/NCI NIH HHS; R01 DE019126/DE/NIDCR NIH HHS; R01 DE019126-01A1/DE/NIDCR NIH HHS
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p57; 0/Receptor, Galanin, Type 2; 136601-57-5/Cyclin D1; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 3.4.22.-/Caspase 3

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