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p130/pRb2 Has Growth Suppressive Properties Similar to yet Distinctive from Those of Retinoblastoma Family Members pRb and p107¹

Departments of Pathology and Biochemistry, Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140 [P. P. C., C. M. H., A. B., A. D. L., Y. F., A. G.]; Jefferson Cancer Institute and Thomas Jefferson University, Philadelphia Pennsylvania 19107 [G. C., B. C.] and Cell Biology Section, Laboratory of Viral Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702 [Y. S., N. C.]

The retinoblastoma tumor suppressor gene product, as well as its related protein p107, has been shown clearly to exert its growth suppressive effects in a cell cycle dependent manner. In this study we demonstrate that the introduction of our recently cloned Rb family member p130/pRb2 causes growth arrest in three tumor cell lines. In addition, in the nasopharyngeal carcinoma derived cell line HONE-1, we identified a low level of expression of p130/pRb2, possibly due to gene rearrangement, and a drastic reduction in proliferation upon introduction of a constitutive active p130/pRb2 complementary DNA clone. Furthermore, we were able to dissect distinct properties of the Rb family by demonstrating that p130/pRb2 inhibits proliferation of the glioblastoma cell line T98G, which is resistant to the growth suppressive effects of both pRb and p107. Our studies demonstrate that the Rb family proteins identified to date may complement each other but they are not fully functionally redundant.

¹ A. D. L. is supported by a fellowship from the University of Bari (Dottorato di Ricerca in Morfologia Umana e Sperimentale). The work was supported by NIH Grant RO1 CA60999 and a grant from W. W. Smith to A. G. and American Cancer Society grants to B. C.

² To whom requests for reprints should be addressed. Present address: Institute for Cancer Research and Molecular Medicine and Jefferson Cancer Institute, Thomas Jefferson University, Bluemle Life Sciences Bldg., 233 South 10th St., Philadelphia, PA 19107.

Received 9/16/94. Accepted 9/29/94.

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