Abstract
Alternative use of genes of the closely-related pp32 family is a common occurrence in human prostate cancer. pp32r1 and pp32r2, the oncogenic members of the pp32 family, are expressed in prostatic adenocarcinoma, while adjacent benign prostate continues to express pp32. This study focuses upon the role of pp32 in tumor suppression. We demonstrate that antisense inhibition of pp32 in NIH3T3 cells leads to a variety of phenotypic changes associated with transformation including reduced serum dependence and loss of contact inhibition. NIH3T3 cells with antisense-inhibited pp32 are not tumorigenic, but are markedly more susceptible to oncogenic stimuli such as ras. In contrast, constitutive expression of pp32 abolishes ras mediated transformation in vitro and tumorigenesis in vivo. These data demonstrate, from the functional aspect, that pp32 acts as a tumor suppressor. Furthermore, inactivation of pp32 function through alternative gene use may be a critical event in tumor evolution and progression.
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Acknowledgements
We thank Dr W Pan for generous help and advice; Drs S Baylin, C Dang, D Pardoll, D Borchelt, M Mahmoud and E Saria for critical reading of the manuscript; and Mr T Eshetu for expert technical support. Supported by United States Public Health Service Grant RO1 CA54404 to GR Pasternack and Komen National Research Award 99-003275 to J Bai.
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Bai, J., Brody, J., Kadkol, S. et al. Tumor suppression and potentiation by manipulation of pp32 expression. Oncogene 20, 2153–2160 (2001). https://doi.org/10.1038/sj.onc.1204294
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DOI: https://doi.org/10.1038/sj.onc.1204294
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