Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma.
Mutational inactivation of the retinoblastoma gene (RB) is found in all retinoblastomas and in a subset of other human neoplasms, including sarcomas of bone or soft tissue and carcinomas of lung or breast. Exogenous copies of wild-type RB have been shown to suppress the tumorigenicity of several types of tumor cells with endogenous RB mutations, including a previously described human prostatic carcinoma cell line. To further support a role for RB inactivation in the genesis of prostate cancer, seven primary or metastatic prostate carcinoma specimens were examined for evidence of RB mutation. By the use of immunoblot analysis and immunostaining of histologic sections, RB-encoded protein was readily detected in tumor cells of five specimens, was equivocally detected in one specimen, and was apparently absent from tumor cells of one specimen. RB mutations in the latter case were precisely characterized as (i) a deletion of 103 nucleotides containing transcriptional start sites and (ii) loss of the second RB allele. The 103-base-pair deletion was sufficient to abolish the promoter activity of upstream DNA sequences in a heterologous expression system. These results (i) demonstrate that RB can be inactivated in vivo by mutation of its promoter, (ii) confirm the existence of RB mutations in some human prostate carcinomas, and (iii) suggest the use of immunohistochemical methods to screen for RB mutations in clinical samples of common adult neoplasms.
Bookstein
R
R
Department of Pathology, University of California, San Diego, La Jolla 92093-0612.
Rio
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Madreperla
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Hong
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Allred
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Grizzle
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Lee
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D001344:Autopsy; D001483:Base Sequence; D001706:Biopsy; D002872:Chromosome Deletion; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D016160:Retinoblastoma Protein / Q000032:analysis / Q000235:genetics*
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D016160:Retinoblastoma Protein