Frequent genetic alterations and reduced expression of the Axin1 gene in oral squamous cell carcinoma: involvement in tumor progression and metastasis.
Article Details
- CitationCopy to clipboard
Zhou CX, Gao Y
Frequent genetic alterations and reduced expression of the Axin1 gene in oral squamous cell carcinoma: involvement in tumor progression and metastasis.
Oncol Rep. 2007 Jan;17(1):73-9.
- PubMed ID
- 17143481 [ View in PubMed]
- Abstract
The aims of this study were to analyze the genetic alterations and expression levels of the Axin1 gene in oral squamous cell carcinoma (OSCC), to evaluate its clinical importance and to clarify whether the Axin1 gene is involved in the pathogenesis of OSCC. Mutation analysis of the Axin1 gene was performed by denaturing high performance liquid chromatography (DHPLC) and DNA sequencing in 44 OSCC samples. Meanwhile, Axin1 protein expression was investigated by immunohistochemistry in these samples. Aberrant profiles were detected by DHPLC screening in 26 different OSCC cases. After sequencing analysis, four mutations and five polymorphisms were identified. One case of poorly differentiated OSCC with metastasis contained two mutations: one revealed a T>G substitution at nucleotide 324 in exon 1, resulting in a glycine to stop codon substitution at amino acid residue 108; the other revealed an A>G heterozygous mutation in intron 7, located very near to exon 8. In another two patients with moderately differentiated OSCC and metastasis, a G>T heterozygous mutation at codon 488 in exon 5 and a C>G substitution at the intron 5+26 position was detected, respectively. Five polymorphisms were all frequent and localized at positions of codon 254 (GAT--> GAC), codon 429 (GTC-->ATC), codon 525 (GAC-->GAT), codon 609 (GCT--> GCC), and intron 4+17 (G>A), with a frequency of 39%, 8%, 6%, 13% and 9%, respectively. Immunoreactivity for Axin1 was strongly positive in normal stratified squamous epithelium but significantly reduced expression of Axin1 was shown in most of the 44 tumor specimens (35/44), especially in poorly differentiated tumors with metastasis. These results suggest that mutational inactivation and reduced expression of the Axin1 gene may play a pivotal role in OSCC carcinogenesis and metastasis.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Glycine Glycine N-acyltransferase Protein Humans UnknownSubstrateDetails