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GENES & DEVELOPMENT 18:2952-2962, 2004
©2004 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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RESEARCH PAPER

Tissue-specific tumor suppressor activity of retinoblastoma gene homologs p107 and p130

Jan-Hermen Dannenberg1, Leontine Schuijff, Marleen Dekker, Martin van der Valk and Hein te Riele2

Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

The retinoblastoma gene family consists of three genes: RB, p107, and p130. While loss of pRB causes retinoblastoma in humans and pituitary gland tumors in mice, tumorigenesis in other tissues may be suppressed by p107 and p130. To test this hypothesis, we have generated chimeric mice from embryonic stem cells carrying compound loss-of-function mutations in the Rb gene family. We found that Rb/p107- and Rb/p130-deficient mice were highly cancer prone. We conclude that in a variety of tissues tumor development by loss of pRB is suppressed by its homologs p107 and p130. The redundancy of the retinoblastoma proteins in vivo is reflected by the behavior of Rb-family-defective mouse embryonic fibroblasts in vitro.

[Keywords: Retinoblastoma; cancer; mouse model; pocket proteins]

Received September 10, 2003; revised version accepted September 15, 2004.

Supplemental material is available at http://www.genesdev.org.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.322004.

1 Present address: Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine and Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.

2 Corresponding author.
E-MAIL h.t.riele{at}nki.nl; FAX 31-20-669-1383


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