Related Experiment Videos
THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma
Hong Lok Lung1, Dhinoth Kumar Bangarusamy, Dan Xie
1Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (SAR), People's Republic of China.
Abstract:
Using oligonucleotide microarray analysis, THY1, mapping close to a previously defined 11q22-23 nasopharyngeal carcinoma (NPC) critical region was identified as showing consistent downregulated expression in the tumour segregants, as compared to their parental tumour-suppressing microcell hybrids (MCHs). Gene expression and protein analyses show that THY1 was not expressed in the NPC HONE1 recipient cells, tumour segregants, and other NPC cell lines; THY1 was exclusively expressed in the non-tumourigenic MCHs. The mechanism of THY1 gene inactivation in these cell lines was attributed to hypermethylation. Clinical study showed that in 65% of NPC specimens there was either downregulation or loss of THY1 gene expression. Using a tissue microarray and immunohistochemical staining, 44% of the NPC cases showed downregulated expression of THY1 and 9% lost THY1 expression. The frequency of THY1 downregulated expression in lymph node metastatic NPC was 63%, which was significantly higher than in the primary tumour (33%). After transfection of THY1 gene into HONE1 cells, a dramatic reduction of colony formation ability was observed. These findings suggest that THY1 is a good candidate tumour suppressor gene in NPC, which is significantly associated with lymph node metastases.
Insights
THY1 gene expression is downregulated in nasopharyngeal carcinoma (NPC), suggesting it acts as a tumor suppressor. Loss of THY1 is linked to lymph node metastasis in NPC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Nasopharyngeal carcinoma (NPC) is a significant health concern.
- Identifying novel tumor suppressor genes is crucial for understanding NPC development.
- The 11q22-23 region is implicated in NPC critical regions.
Purpose of the Study:
- To investigate the role of THY1 as a potential tumor suppressor gene in NPC.
- To analyze the expression patterns of THY1 in NPC cell lines and clinical specimens.
- To determine the association between THY1 expression and NPC metastasis.
Main Methods:
- Oligonucleotide microarray analysis to identify differentially expressed genes.
- Gene expression and protein analysis in NPC cell lines and microcell hybrids.
- Analysis of THY1 methylation status.
- Tissue microarray and immunohistochemical staining on NPC patient samples.
- Functional studies involving THY1 gene transfection.
Main Results:
- THY1 expression was consistently downregulated in NPC tumor segregants compared to parental tumor-suppressing microcell hybrids.
- THY1 was not expressed in NPC cell lines but exclusively in non-tumourigenic cells.
- Hypermethylation was identified as the mechanism for THY1 gene inactivation.
- Downregulation or loss of THY1 expression was observed in 65% of NPC specimens.
- Significantly higher frequency of THY1 downregulation in lymph node metastatic NPC (63%) versus primary tumors (33%).
- Transfection of THY1 into NPC cells reduced colony formation ability.
Conclusions:
- THY1 functions as a candidate tumor suppressor gene in nasopharyngeal carcinoma.
- THY1 downregulation is significantly associated with lymph node metastasis in NPC.
- Restoration of THY1 expression may offer a therapeutic strategy for NPC.
Related Concept Videos
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:39lncRNA - Long Non-coding RNAs
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...