title: Aberrant activation of hedgehog pathway in nasopharyngeal carcinoma.
abstract: Nasopharyngeal carcinoma (NPC) is a very common head and neck cancer in southern china. Despite advances in surgical and chemotherapeutic approaches, its prognosis is still not promising. Hedgehog signaling pathway was reported to be involved in a number of cancers including head and neck. However, it remains unclear regarding the role of this pathway in NPC. By real-time PCR, we found Ptch1, Smo, and Gli-1 were expressed in all human nasopharyngeal epithelial tissues and cell lines. Compared with nasopharyngeal normal epithelial tissues, the mRNA expression level of Gli-1 was higher in carcinoma and nasopharyngitis (NPI) epithelial tissues. While compared with nasopharyngitis epithelia, the mRNA expression level of Ptch1 was lower in carcinoma epithelia and normal epithelia. The expressions of Smo mRNA were not significantly different among these epithelial tissues. Immunohistochemistry analysis revealed that the expression level of Gli-1 was higher in NPC than NPI. Thus, our data indicated that aberrant activation of hedgehog pathway in NPC. Furthermore, blocking the pathway with cyclopamine inhibited the proliferation of NPC epithelia cell lines. In addition, blockade of the pathway in three NPC cell lines with cyclopamine-induced tumor cell apoptosis. The transcription of hedgehog target genes also is inhibited by cyclopamine. These data suggested that hedgehog pathway may sustain nasopharyngeal tumor growth. Our data demonstrated that hedgehog signaling pathway was involved in NPC pathogenesis and might be a novel therapeutic target for NPC.
authors.affiliation: Life Science College, Sun Yat-sen University, No. 135 Xingang xi Road, Guangzhou, 510275, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Yue
authors.forename: Weide
authors.initials: W
authors.lastname: Zhong
authors.forename: Genwang
authors.initials: G
authors.lastname: Pei
authors.forename: Baiyu
authors.initials: B
authors.lastname: Xiao
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhang
authors.forename: Funeng
authors.initials: F
authors.lastname: Jiang
authors.forename: Jinglin
authors.initials: J
authors.lastname: Zhang
authors.forename: Changhua
authors.initials: C
authors.lastname: Chen
authors.forename: Peizhou
authors.initials: P
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Dang
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000378:metabolism; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis*; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002681:China; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000503:physiopathology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000032:analysis*; D043562:Receptors, G-Protein-Coupled / Q000032:analysis*; D015398:Signal Transduction; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000032:analysis*; D014704:Veratrum Alkaloids / Q000378:metabolism; D055815:Young Adult; D000071676:Zinc Finger Protein GLI1
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; C400551:GLI1 protein, human; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; C000541:cyclopamine