title: Reduced L/B/K alkaline phosphatase gene expression in renal cell carcinoma: plausible role in tumorigenesis.
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.
authors.affiliation: Department of Biochemistry, PGIMER, Chandigarh, India.
authors.forename: Ujjawal
authors.initials: U
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, PGIMER, Chandigarh, India.
authors.forename: Deeksha
authors.initials: D
authors.lastname: Pal
authors.affiliation: Department of Urology, PGIMER, Chandigarh, India.
authors.forename: Shrawan Kumar
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Department of Histopathology, PGIMER, Chandigarh, India.
authors.forename: Nandita
authors.initials: N
authors.lastname: Kakkar
authors.affiliation: Department of Biochemistry, PGIMER, Chandigarh, India. Electronic address: fateh1977@yahoo.com.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Prasad
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001842:Bone and Bones / Q000201:enzymology; D063646:Carcinogenesis; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000469:Alkaline Phosphatase
keywords: Alkaline phosphatase; Apoptosis; Cell lines; Renal cell carcinoma; Transfection