title: The FHIT gene product is highly expressed in the cytoplasm of renal tubular epithelium and is down-regulated in kidney cancers.
abstract: Loss of heterozygosity and homozygous deletion of the 3p14.2 region in human cancers implies the existence of a tumor suppressor gene. One such candidate is the fragile histidine triad (FHIT) gene. To investigate the role of FHIT gene product in tumorigenesis, we generated specific polyclonal antibodies to the human protein and studied its expression in normal and tumor tissues. Immunoblot analysis revealed highly variable expression of pFhit in normal adult human tissues. The highest steady-state level of pFhit was found in kidney and brain, whereas breast, intestine, and skeletal muscle expressed only trace amounts. Within the kidney, the pattern of pFhit immunoreactivity was confined to the tubular epithelium and absent in the glomeruli. Immunofluorescence analysis and biochemical fractionation have sublocalized pFhit to the cytosolic compartment. Compared with normal kidney, pFhit was found to be down-regulated in a subset of primary renal cell carcinoma. Two of 12 renal cell carcinoma cell lines that are known not to contain VHL mutations showed complete loss of pFhit expression. This is supported by the appearance of aberrant reverse transcription-polymerase chain reaction products and loss of the normal-size fragment. Our results are consistent with a potential role of pFhit loss or dysfunction in human renal cell carcinoma independent of VHL involvement.
authors.affiliation: Division of Medical Sciences, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: G H
authors.initials: GH
authors.lastname: Xiao
authors.forename: F
authors.initials: F
authors.lastname: Jin
authors.forename: A J
authors.initials: AJ
authors.lastname: Klein-Szanto
authors.forename: T L
authors.initials: TL
authors.lastname: Goodrow
authors.forename: M W
authors.initials: MW
authors.lastname: Linehan
authors.forename: R S
authors.initials: RS
authors.lastname: Yeung
mesh_terms: D017766:Acid Anhydride Hydrolases; D014408:Biomarkers, Tumor; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002461:Cell Line, Transformed; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation; D004848:Epithelium / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006367:HeLa Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D011506:Proteins; D000099170:Bis(5'-adenosyl)triphosphatase