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Sympathectomy suppresses tumor growth and alters gene‐expression profiles in rat tongue cancer
Author(s) -
Raju Bina,
Hultström Michael,
Haug Sivakami R.,
Ibrahim Salah O.,
Heyeraas Karin J.
Publication year - 2009
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/j.1600-0722.2009.00646.x
Subject(s) - carcinogenesis , biology , gene expression , microarray , tongue , microarray analysis techniques , gene , angiogenesis , sympathectomy , denervation , pathology , cancer research , endocrinology , medicine , genetics
Sympathetic nerves are known to affect carcinogenesis. Recently we found that sympathetic denervation decreases the size of rat tongue tumors. To identify genes involved in rat tongue carcinogenesis and to study the effect of sympathetic nerves on these genes, we compared gene‐expression profiles in normal rat tongue (control) and in tumor‐induced tongues with (SCGx) and without (Sham) bilateral sympathectomy. Significance analysis of microarrays revealed 280 genes (168 up‐regulated, 112 down‐regulated) that showed at least a twofold differential expression between Sham and SCGx tumors (false discovery rate < 5%). These included genes associated with cell adhesion, signaling, structure, proliferation, metabolism, angiogenesis, development, and immunity. Hierarchical clustering demonstrated that controls and sympathectomized tumors grouped together, while Sham tumors grouped separately. We identified 34 genes, known to be involved in carcinogenesis, that were not differentially expressed between sympathectomized tumors and control tongues, but which showed a significant change in expression in Sham tumors. Microarray results of 12 of these genes were confirmed by quantitative reverse transcription–polymerase chain reaction. In conclusion, sympathectomy significantly altered the gene‐expression profile and inhibited tumor growth. The expression of several cancer genes were increased more than threefold in Sham tumors, but unaltered in the sympathectomized tumors when compared with controls, indicating that these genes may be of significance in rat tongue carcinogenesis.