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Reduced L/B/K alkaline phosphatase gene expression in renal cell carcinoma: plausible role in tumorigenesis
Ujjawal Sharma1, Deeksha Pal1, Shrawan Kumar Singh2
1Department of Biochemistry, PGIMER, Chandigarh, India.
Abstract:
Renal cell carcinoma (RCC) is the most common kidney cancer in adults. Although several genes have been found to be involved in carcinogenesis of RCC, more great efforts are needed to identify new genes which are responsible for the process. Clear cell RCC, originates from proximal tubule cells, is the most common pathological type of RCC. Alkaline phosphatase (ALP) is a marker enzyme of brush border membrane of proximal tubular cells. Our previous studies showed a significant decreased activity of Liver/Bone/Kidney (L/B/K) alkaline phosphatase in RCC. In the present study, we explored the molecular basis of the decreased activity of ALP in RCC. Immunohistochemistry, immunofluorescence and flow cytometry analysis showed decreased ALP protein in RCC. Additionally, real time PCR documented significantly reduced ALP gene expression (P = 0.009). Moreover, RCC cell lines (ACHN and A498) transfected with full length L/B/K cDNA showed decreased migratory property as well as viability of these cells as compared with controls (P = 0.000). Further, L/B/K ALP cDNA transfected cells (ACHN and A498) showed significant increased apoptosis as compared to control (P = 0.000). These findings suggest the new role of ALP in cell viability and apoptosis and involvement in RCC tumorigenesis. However, further studies are needed to explore the exact molecular mechanism.
Insights
Reduced activity of Liver/Bone/Kidney alkaline phosphatase (ALP) in renal cell carcinoma (RCC) is linked to decreased cell viability and increased apoptosis. Further research is needed to understand ALP's role in kidney cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Renal cell carcinoma (RCC) is the most prevalent kidney cancer in adults.
- Identifying novel genes involved in RCC carcinogenesis remains crucial.
- Liver/Bone/Kidney alkaline phosphatase (ALP) is a marker for proximal tubular cells, and its activity is decreased in RCC.
Purpose of the Study:
- To investigate the molecular basis for the reduced activity of ALP in RCC.
- To explore the potential role of ALP in RCC cell viability, migration, and apoptosis.
Main Methods:
- Immunohistochemistry, immunofluorescence, and flow cytometry to assess ALP protein levels.
- Real-time PCR to quantify ALP gene expression.
- Transfection of RCC cell lines (ACHN, A498) with L/B/K ALP cDNA to evaluate effects on cell properties.
Main Results:
- Decreased ALP protein expression and significantly reduced ALP gene expression were observed in RCC.
- Transfection with L/B/K ALP cDNA led to decreased cell viability and migration in RCC cell lines.
- Significant increase in apoptosis was noted in RCC cells transfected with L/B/K ALP cDNA.
Conclusions:
- The findings suggest a novel role for ALP in regulating cell viability and apoptosis.
- ALP appears to be involved in the tumorigenesis of RCC.
- Further studies are required to elucidate the precise molecular mechanisms underlying ALP's function in RCC.
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