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Published on: January 21, 2012
Analysis of retinoblastoma (RB) gene deletion in human prostatic carcinomas
1Department of Pathology, Wayne State University, School of Medicine, Detroit, MI 48201.
Abstract:
The retinoblastoma tumor suppressor gene (RB gene) has been reported to be deleted and/or modified in a number of human cancers, indicating that dysfunction of this tumor suppressor gene is perhaps critical in the development of many human tumors. In addition to deletion of one copy and/or mutational inactivation of the RB gene, this gene has also been reported to be altered by a small deletion in the promoter sequence in one case of small cell mixed adenocarcinoma of the prostate. A deletion of 105 nucleotides of the RB gene in exon 21, leading to an aberrant short-sized mRNA transcript, has also been reported in one cell line (DU 145) derived from brain metastasis of prostatic adenocarcinoma. We have analyzed tissues from 10 prostate specimens (3 hyperplastic and 7 neoplastic) and one prostate cancer cell line (DU 145) for the presence of short-sized mRNA transcript (exon 21 alterations) by polymerase chain reaction (PCR) using total RNA extracted from frozen tumors and the cell line. None of the prostate tissue showed any evidence of aberrant short-sized mRNA, although it was confirmed in the DU 145 cell line. Simultaneously, we have used DNA-PCR to investigate RB promoter deletion in 23 adenocarcinomas and one small cell carcinoma of the prostate. We also failed to demonstrate any indication of RB promoter deletion at the DNA level in adenocarcinomas. The single case of small cell carcinoma failed to show evidence of any aberration in RB promoter. We therefore conclude that neither RB promoter alterations nor the exon 21 deletion are associated with typical prostate adenocarcinoma.
Insights
Retinoblastoma (RB) gene alterations, including promoter deletions and exon 21 deletions, are not associated with typical prostate adenocarcinoma. These specific RB gene changes were not found in most prostate cancer tissues studied.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The retinoblastoma tumor suppressor gene (RB gene) is crucial in preventing cancer development.
- RB gene dysfunction, through deletions or mutations, is implicated in various human cancers.
- Previous studies suggested RB gene alterations in prostate cancer, including promoter and exon deletions.
Purpose of the Study:
- To investigate the association of RB gene promoter alterations and exon 21 deletions with prostate adenocarcinoma.
- To determine if specific RB gene modifications are present in prostate cancer tissues and cell lines.
Main Methods:
- Polymerase chain reaction (PCR) was used to analyze RNA for short-sized mRNA transcripts (exon 21 alterations).
- DNA-PCR was employed to detect RB promoter deletions in prostate cancer specimens.
- Total RNA and DNA were extracted from prostate tissue samples and the DU 145 cell line.
Main Results:
- No evidence of aberrant short-sized mRNA (exon 21 alterations) was found in the 10 prostate tissue specimens.
- The DU 145 prostate cancer cell line confirmed the presence of the short-sized mRNA transcript.
- No RB promoter deletions were detected in the DNA of 23 prostate adenocarcinomas or one small cell carcinoma.
Conclusions:
- Neither RB promoter alterations nor exon 21 deletions are associated with typical prostate adenocarcinoma.
- The findings suggest these specific RB gene aberrations are not common drivers in the development of this cancer type.
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