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Science 9 February 1990:
Vol. 247. no. 4943, pp. 712 - 715
DOI: 10.1126/science.2300823
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Articles

Science, Vol 247, Issue 4943, 712-715
Copyright © 1990 by American Association for the Advancement of Science

articles

Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene

R Bookstein, JY Shew, PL Chen, P Scully, and WH Lee

Department of Pathology, School of Medicine, University of California, San Diego, La Jolla 92093.

Introduction of a normal retinoblastoma gene (RB) into retinoblastoma cells was previously shown to suppress several aspects of their neoplastic phenotype, including tumorigenicity in nude mice, thereby directly demonstrating a cancer suppression function of RB. To explore the possibility of a similar activity in a common adult tumor, RB expression was examined in three human prostate carcinoma cell lines. One of these, DU145, contained an abnormally small protein translated from an RB messenger RNA transcript that lacked 105 nucleotides encoded by exon 21. To assess the functional consequences of this mutation, normal RB expression was restored in DU145 cells by retrovirus-mediated gene transfer. Cells that maintained stable exogenous RB expression lost their ability to form tumors in nude mice, although their growth rate in culture was apparently unaltered. These results suggest that RB inactivation can play a significant role in the genesis of a common adult neoplasm and that restoration of normal RB-encoded protein in tumors could have clinical utility.


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T Mahdi, A Brizard, C Millet, P Dore, J Tanzer, and A Kitzis (1995)
J. Cell Sci. 108, 1287-1293
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Disruption of retinoblastoma protein function by coexpression of its C pocket fragment..
P J Welch and J Y Wang (1995)
Genes & Dev. 9, 31-46
   Abstract »    PDF »
Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53..
K A Howes, N Ransom, D S Papermaster, J G Lasudry, D M Albert, and J J Windle (1994)
Genes & Dev. 8, 1300-1310
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Growth Suppression by Members of the Retinoblastoma Protein Family.
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Cold Spring Harb Symp Quant Biol 59, 75-84
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The Corral Hypothesis: A Novel Regulatory Mode for Retinoblastoma Protein Function.
W.-H. Lee, Y. Xu, F. Hong, T. Durfee, M.A. Mancini, Y.-C. Ueng, P.-L. Chen, and D. Riley (1994)
Cold Spring Harb Symp Quant Biol 59, 97-107
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Genetic Alterations in Prostate Cancer.
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Cold Spring Harb Symp Quant Biol 59, 653-659
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WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant.
D. Haber, S Park, S Maheswaran, C Englert, G. Re, D. Hazen-Martin, D. Sens, and A. Garvin (1993)
Science 262, 2057-2059
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Expression of a retinoblastoma transgene results in dwarf mice..
Y J Bignon, Y Chen, C Y Chang, D J Riley, J J Windle, P L Mellon, and W H Lee (1993)
Genes & Dev. 7, 1654-1662
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Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein..
L Zhu, S van den Heuvel, K Helin, A Fattaey, M Ewen, D Livingston, N Dyson, and E Harlow (1993)
Genes & Dev. 7, 1111-1125
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The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit..
T Durfee, K Becherer, P L Chen, S H Yeh, Y Yang, A E Kilburn, W H Lee, and S J Elledge (1993)
Genes & Dev. 7, 555-569
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E2F: a link between the Rb tumor suppressor protein and viral oncoproteins.
Nevins JR (1992)
Science 258, 424-429
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Identification of a growth suppression domain within the retinoblastoma gene product..
X Q Qin, T Chittenden, D M Livingston, and W G Kaelin (1992)
Genes & Dev. 6, 953-964
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The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F..
S W Hiebert, S P Chellappan, J M Horowitz, and J R Nevins (1992)
Genes & Dev. 6, 177-185
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Tumor suppressor genes.
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Science 254, 1138-1146
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Expression of the Wilms' tumor gene WT1 in the murine urogenital system..
J Pelletier, M Schalling, A J Buckler, A Rogers, D A Haber, and D Housman (1991)
Genes & Dev. 5, 1345-1356
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Medical Genetics.
M. R. Hughes and C. T. Caskey (1991)
JAMA 265, 3132-3134
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Senescence of nickel-transformed cells by an X chromosome: possible epigenetic control.
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Science 251, 796-799
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c-myc and pRB: Role in TGF-{beta}1 Inhibition of Keratinocyte Proliferation.
C.S. Murphy, J.A. Pietenpol, K. Munger, P.M. Howley, and H.L. Moses (1991)
Cold Spring Harb Symp Quant Biol 56, 129-135
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Cold Spring Harb Symp Quant Biol 56, 197-209
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Genetic mechanisms of tumor suppression by the human p53 gene.
P. Chen, Y. Chen, R Bookstein, and W. Lee (1990)
Science 250, 1576-1580
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Antisense RNA-mediated Deficiency of the Calpain Protease, nCL-4, in NIH3T3 Cells Is Associated with Neoplastic Transformation and Tumorigenesis.
K. Liu, L. Li, and S. N. Cohen (2000)
J. Biol. Chem. 275, 31093-31098
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Neoplastic Transformation and Tumorigenesis Associated with Sam68 Protein Deficiency in Cultured Murine Fibroblasts.
K. Liu, L. Li, P. E. Nisson, C. Gruber, J. Jessee, and S. N. Cohen (2000)
J. Biol. Chem. 275, 40195-40201
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ANX7, a candidate tumor suppressor gene for prostate cancer.
M. Srivastava, L. Bubendorf, V. Srikantan, L. Fossom, L. Nolan, M. Glasman, X. Leighton, W. Fehrle, S. Pittaluga, M. Raffeld, et al. (2001)
PNAS 98, 4575-4580
   Abstract »    Full Text »    PDF »


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