Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma

Journal Article · Mon Oct 01 04:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.19.7762· OSTI ID:5544085

Bookstein, R; Rio, P; Madreperla, S A; Hong, F; Lee, W H ^[1]; Allred, C ^[2]; Grizzle, W E ^[3]

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1. Univ. of California at San Diego, La Jolla (USA)
2. The Univ. of Texas Health Sciences Center at San Antonio, TX (USA)
3. Univ. of Alabama at Birmingham (USA)

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 immunohistochemcial methods to screen for RB mutations in clinical samples of common adult neoplasms.

• OSTI ID: 5544085
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:19; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BIOCHEMISTRY
BODY
CARCINOMAS
CHEMISTRY
CYTOCHEMISTRY
DISEASES
ETIOLOGY
GENE REGULATION
GENE REPRESSORS
GENES
GLANDS
INACTIVATION
MALE GENITALS
MAMMALS
MAN
NEOPLASMS
NUCLEOPROTEINS
ORGANIC COMPOUNDS
ORGANS
PRIMATES
PROSTATE
PROTEINS
TUMOR CELLS
VERTEBRATES