title: Differential expression of hedgehog signaling components and Snail/E-cadherin in human brain tumors.
abstract: The hedgehog (Hh) transcription factor Gli induces transformation of epithelial cells via induction of Snail, a repressor of E-cadherin. Epithelial-mesenchymal transition is also a determinant of the progression of tumorigenesis, following down-regulation of E-cadherin. However, the role of Hh signaling components and Snail/E-cadherin in brain tumors is not yet fully understood. We analyzed the expression of Hh signaling components and Snail/E-cadherin in 69 brain tumors by reverse transcription-polymerase chain reaction (RT-PCR). The data showed that overexpression of Smo (35/69), Ptch (50/69), Gli1 (56/69), Gli2 (29/69) and N-myc (39/69) might contribute to brain tumorigenesis. Our results also indicated that Snail and E-cadherin showed opposing expression in malignant tumors (high grade astrocytoma and metastasis). Snail and E-cadherin showed less correlation in benign brain tumors. We further investigated mutations of Gli2 and Snail by RT-PCR and direct sequencing. No mutation was observed on Gli2 but several sporadic mutations on Snail were found, including S96G, S111L, S111L/S119Y and one nonsense mutation at codon 158 (Y158*). An in vitro E-cadherin promoter assay showed that S96G, S111L, S111L/S119Y Snail mutants were decreased by 15, 25 and 50%, respectively, whereas Y158* was increased by 40% compared to wild-type. Furthermore, our data showed that wild-type Snail and S96G, S111L, S111L/S119Y translocated to the nucleus, while the Y158* mutant failed to translocate to the nucleus. Taken together, our results demonstrate that Hh signaling components, the expression and mutations of Snail and the expression of E-cadherin may play an important role in human brain tumorigenesis.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Chou
authors.forename: Ann-Shung
authors.initials: AS
authors.lastname: Lieu
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Wu
authors.forename: Li-Kwan
authors.initials: LK
authors.lastname: Chang
authors.forename: Joon-Khim
authors.initials: JK
authors.lastname: Loh
authors.forename: Run-Chin
authors.initials: RC
authors.lastname: Lin
authors.forename: Wei-Jay
authors.initials: WJ
authors.lastname: Chen
authors.forename: Huei-De
authors.initials: HD
authors.lastname: Liao
authors.forename: Wen-Shane
authors.initials: WS
authors.lastname: Fu
authors.forename: Chung-Shing
authors.initials: CS
authors.lastname: Chang
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Lin
authors.forename: Ching-Mei
authors.initials: CM
authors.lastname: Hsu
authors.forename: Chung-Ching
authors.initials: CC
authors.lastname: Chio
authors.forename: Shen-Long
authors.initials: SL
authors.lastname: Howng
authors.forename: Yi-Ren
authors.initials: YR
authors.lastname: Hong
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
chemical_list: D015820:Cadherins; D053823:Hedgehog Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors