Expression of Pax-2 in human renal cell carcinoma and growth inhibition by antisense oligonucleotides.
Renal cell carcinoma (RCC) is the most common malignancy in the adult kidney. Because RCC is generally thought to arise from the epithelium of the proximal tubules, the expression of Pax-2, a gene required for renal epithelium development, was examined in primary tumors and tumor-derived cell lines. Immunostaining of frozen sections from the primary tumors indicated Pax-2 expression in the malignant cells but not in the surrounding stroma. In a panel of human RCC-derived cell lines, 73% expressed Pax-2 protein and mRNA. Treatment of RCC cell lines with antisense oligodeoxynucleotides resulted in down-regulation of Pax-2 protein expression and growth inhibition after 3 days in culture. These data indicate that Pax-2 gene function is required for proliferation, as well as differentiation during embryonic development, and suggest a novel therapy for RCC.
Gnarra
J R
JR
Urological Oncology Section, National Cancer Institute, Bethesda, Maryland 20892, USA.
Dressler
G R
GR
D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D051762:PAX2 Transcription Factor; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors