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Published on: July 22, 2020
Identification of THW, a putative new tumor suppressor gene
T Hildebrandt1, J Preiherr, N Tarbé
1Roche Diagnostics GmbH, Pharma Research, Penzberg, Germany.
Abstract:
Differential Display between metastasizing and non-metastasizing human melanoma cell lines NMCL-1 and 530 led to the identification of a putative transmembrane receptor, designated as THW, which is down-regulated in the metastasizing cell line. THW is composed of 193 aa, exhibits four putative transmembrane domains and does not reveal any homology to other proteins. Down-regulation of THW is correlated with metastatic capacity of melanoma cell lines. THW was down-regulated in mammary carcinoma cell lines compared with cell lines derived from non-malignant mammary epithelium, in pancreas cell lines derived from metastases compared with a cell line derived from a primary tumor and in several tumor tissues compared with normal tissues. The function of THW as a tumor suppressor is emphasized by the location of the THW gene on chromosome 6q. LOH for this region has been reported in malignant melanoma and prostate, pancreas, uterine and mammary carcinomas.
Insights
A novel transmembrane receptor, THW, is down-regulated in metastasizing melanoma and other cancers. This down-regulation correlates with tumor spread, suggesting THW acts as a tumor suppressor.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastasis is a complex process involving genetic and molecular alterations.
- Identifying genes associated with metastasis is crucial for understanding cancer progression.
Purpose of the Study:
- To identify novel genes involved in melanoma metastasis.
- To investigate the role of the identified gene, THW, in various cancer types.
Main Methods:
- Differential display technique was used to compare gene expression between metastasizing and non-metastasizing melanoma cell lines.
- Bioinformatic analysis was performed to characterize the identified gene (THW).
- Expression levels of THW were analyzed in various cancer cell lines and tissues.
Main Results:
- A novel transmembrane receptor, THW, was identified and found to be down-regulated in metastasizing melanoma cells.
- THW down-regulation was correlated with metastatic capacity across melanoma cell lines.
- THW was also found to be down-regulated in mammary carcinoma, pancreatic cancer, and other tumor tissues compared to normal counterparts.
- The THW gene is located on chromosome 6q, a region known to undergo loss of heterozygosity (LOH) in several cancers.
Conclusions:
- THW functions as a potential tumor suppressor gene.
- Down-regulation of THW is associated with increased metastatic potential in various cancers.
- THW represents a potential therapeutic target for cancer treatment.
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