PROMOTER DELETION AND LOSS OF RETINOBLASTOMA GENE-EXPRESSION IN HUMAN PROSTATE CARCINOMA

被引:338
作者
BOOKSTEIN, R
RIO, P
MADREPERLA, SA
HONG, F
ALLRED, C
GRIZZLE, WE
LEE, WH
机构
[1] UNIV ALABAMA, DEPT PATHOL, BIRMINGHAM, AL 35294 USA
[2] UNIV TEXAS, HLTH SCI CTR, DEPT PATHOL, SAN ANTONIO, TX 78284 USA
关键词
immunohistochemistry; polymerase chain reaction; tumor suppression;
D O I
10.1073/pnas.87.19.7762
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:7762 / 7766
页数:5
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