Level of retinoblastoma protein expression correlates with p16 (MTS-1/INK4A/CDKN2) status in bladder cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-02-04

AUTHORS

William F Benedict, Seth P Lerner, Jain Zhou, Xiaohua Shen, Hideo Tokunaga, Bogdan Czerniak

ABSTRACT

Recent studies have shown that patients whose bladder cancer exhibit overexpression of RB protein as measured by immunohistochemical analysis do equally poorly as those with loss of RB function. We hypothesized that loss of p16 protein function could be related to RB overexpression, since p16 can induce transcriptional downregulation of RB and its loss may lead to aberrant RB regulation. Conversely, loss of RB function has been associated with high p16 protein expression in several other tumor types. In the present study RB negative bladder tumors also exhibited strong nuclear p16 staining while each tumor with strong, homogeneous RB nuclear staining were p16 negative, supporting our hypothesis. To expand on these immunohistochemical studies additional cases were selected in which the status of the p16 encoding gene had been determined at the molecular level. Absent p16 and high RB protein expression was found in the tumors having loss of heterozygosity within 9p21 and a structural change (mutation or deletion) of the remaining p16 encoding gene allele, confirming the staining results. These results strongly support the hypothesis that the RB nuclear overexpression recently associated with poor prognosis in bladder cancer is also associated with loss of p16 function and implies that loss of p16 function could be equally deleterious as RB loss in bladder and likely other cancers. More... »

PAGES

1197-1203

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1202452

DOI

http://dx.doi.org/10.1038/sj.onc.1202452

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012124973

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10022125


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