MDM2 AND p21WAF1/CIP1, WILD-TYPE p53-INDUCED PROTEINS, ARE REGULARLY EXPRESSED BY STERNBERG-REED CELLS IN HODGKIN'S DISEASE
✍ Scribed by SÁNCHEZ-BEATO, MARGARITA; PIRIS, MIGUEL A.; MARTÍNEZ-MONTERO, JUAN C.; GARCÍA, JUAN F.; VILLUENDAS, RAQUEL; GARCÍA, FRANCISCO J.; ORRADRE, JUAN L.; MARTÍNEZ, PEDRO
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 749 KB
- Volume
- 180
- Category
- Article
- ISSN
- 0022-3417
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✦ Synopsis
Mutations in the p53 tumour suppressor gene are the most common genetic alteration found in human cancers. Most of them are accompanied by stabilization of the protein, which renders it detectable through immunohistochemical techniques. Although p53 expression is a very common finding in Hodgkin's disease (HD), the status of the p53 gene is scarcely known, due to the difficulty in sequencing this gene in a lesion in which tumour cells are thought to constitute a very minor subpopulation, diluted in a background of supposedly benign cells. The pattern of expression of two downstream pS3 proteins (MDM2 and p21WAF1~C1P1, was studied as an indirect way of assessing p53 gene status. MDM2 is a wild-pS3 inducible protein which may form a complex with p53, abrogating its function, a s has been found in human sarcomas and other malignancies. pZIWAF1/CIP' is another protein inducible by wild-type p53, involved in inhibiting cell-cycle progression, through binding to cyclinlcyclin-dependent-kinase complexes. MDMZ and p21WAF11C'P' immunostaining was detected in all the cases analysed, independently of histological type, and were mainly present in Sternberg-Reed and Hodgkin (H & SR) cells. These immunohistochemical results were confirmed by Western blotting. To study the cause of MDMZ protein accumulation, MDM2 mRNA expression was also investigated by reverse transcription polymerase chain reaction (RT-PCR). The results show the presence of MDMZ transcripts in all cases of HD, albeit at lower levels than those found in reactive lymphoid tissue. These results seem to support the hypothesis that p53 is transcriptionally active in a t least some of the H & SR cells in HD, and is able to induce MDMZ and p21WAF1'C1P1 protein expression.