Differential expression of hedgehog signaling components and Snail/E-cadherin in human brain tumors
Resource
ONCOLOGY REPORTS, 24(5), 1225-1232
Journal
Oncology Reports
Date Issued
2010
Date
2010
Author(s)
Chou, Chia-Hua
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.
Subjects
Brain tumor; E-cadherin; Hedgehog pathway; Localization; Snail
SDGs
Other Subjects
glycine; leucine; Myc protein; protein Patched; serine; sonic hedgehog protein; transcription factor; transcription factor Gli1; transcription factor Gli2; transcription factor Smo; transcription factor Snail; tyrosine; unclassified drug; uvomorulin; amino acid substitution; article; astrocytoma; brain metastasis; brain tumor; brain tumorigenesis; carcinogenesis; cell nucleus; codon; controlled study; disease severity; gene overexpression; gene sequence; human; human cell; human tissue; in vitro study; major clinical study; meningioma; mutant; neurosurgery; nonsense mutation; priority journal; promoter region; protein expression; protein localization; reverse transcription polymerase chain reaction; signal transduction; site directed mutagenesis; wild type; Brain Neoplasms; Cadherins; Down-Regulation; Gene Expression Regulation, Neoplastic; Hedgehog Proteins; Humans; Mutagenesis, Site-Directed; Point Mutation; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Subcellular Fractions; Transcription Factors
Type
journal article
File(s)![Thumbnail Image]()
Loading...
Name
117.pdf
Size
23.18 KB
Format
Adobe PDF
Checksum
(MD5):c0bfb568a69ad42ca4cf15f445c1ef2b