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Characterization of MAST9/Hevin, a SPARC-like protein, that is down-regulated in non-small cell lung cancer
I Bendik1, P Schraml, C U Ludwig
1Department of Research, University Hospital Basel, Switzerland.
Abstract:
In the search for genes down-regulated in non-small cell lung cancer (NSCLC), we have identified a cDNA fragment, termed MAST9. Cloning, sequencing, and characterization of the full-length MAST9 cDNA revealed that the entire 2808 nucleotide sequence had an open reading frame of 1992 nucleotides encoding a Mr 75,000 protein. Sequence analysis disclosed a striking homology to SPARC, known to be involved in tumorigenesis. The recently identified "Hevin" cDNA isolated from high endothelial venules is identical to MAST9. Using Northern and Western blot analysis, we showed that MAST9 was down-regulated in the tumor samples of nine non-small cell lung carcinoma patients. Furthermore, we demonstrated that both the bacterially expressed and the endogenous MAST9 proteins form homodimers. The lack of expression in non-small cell lung carcinomas and its homology to SPARC suggest a putative role of MAST9 in lung tumor formation.
Insights
Researchers identified MAST9, a gene homologous to SPARC, as down-regulated in non-small cell lung cancer (NSCLC). This finding suggests MAST9 may play a role in lung tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) is a major cause of cancer mortality.
- Identifying genes involved in tumorigenesis is crucial for understanding cancer development.
- SPARC is a known protein implicated in various cancers.
Purpose of the Study:
- To identify genes that are down-regulated in non-small cell lung cancer.
- To characterize the MAST9 gene and its protein product.
- To investigate the potential role of MAST9 in lung cancer.
Main Methods:
- Gene identification and cloning of full-length MAST9 cDNA.
- Sequence analysis and homology comparison to known proteins (SPARC).
- Northern and Western blot analysis to assess gene expression in tumor samples.
- Protein expression and dimerization studies.
Main Results:
- MAST9 cDNA was identified and fully characterized, encoding a 75 kDa protein.
- MAST9 shows significant homology to SPARC, a protein involved in tumorigenesis.
- MAST9 expression was found to be down-regulated in NSCLC tumor samples.
- MAST9 protein forms homodimers.
Conclusions:
- MAST9, also known as Hevin, is down-regulated in non-small cell lung cancer.
- Its homology to SPARC and reduced expression suggest a potential tumor suppressor role for MAST9 in lung cancer.
- Further research into MAST9's function could reveal new therapeutic targets for NSCLC.