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Modulation of oncogenic potential by alternative gene use in human prostate cancer

Nature Medicine volume 5, pages 275–279 (1999)Cite this article

A Correction to this article was published on 01 September 1999

Abstract

Only a small percentage of primary prostate cancers have genetic changes. In contrast, nearly 90% of clinically significant human prostate cancers seems to express high levels of the nuclear phosphoprotein pp32 by in situ hybridization. Because pp32 inhibits oncogene-mediated transformation, we investigated its paradoxical expression in cancer by comparing the sequence and function of pp32 species from paired benign prostate tissue and adjacent prostatic carcinoma from three patients. Here we demonstrate that pp32 is expressed in benign prostatic tissue, but pp32r1 and pp32r2, closely-related genes located on different chromosomes, are expressed in prostate cancer. Although pp32 is a tumor suppressor, pp32r1 and pp32r2 are tumorigenic. Alternative use of the pp32, pp32r1 and pp32r2 genes may modulate the oncogenic potential of human prostate cancer.

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Figure 1: a, Detection of pp32-related mRNA in benign prostate tissue and prostate cancer.
Figure 2: a, Amplification of pp32 and pp32 variants from human prostate cancer.
Figure 3: Alignment of pp32 with human prostate tumor-derived pp32r1 and pp32r2 sequences.
Figure 4: Effect of variant pp32 species on transformation: altered oncogenic potential of pp32r1 and pp32r2.

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References

  1. Isaacs, W.B. et al. Genetic alterations in Prostate Cancer. Cold Spring Harbor Symposia on Quantitative Biology 59, 653– 659 (1994).

    Article  CAS  Google Scholar 

  2. Fleming, W.H., Hamel, A., McDonald, R. & Ramsey, E. Expression of c- myc proto-oncogene in human prostate carcinoma and BPH. Cancer Res. 46, 1535–1538 (1986).

    CAS  PubMed  Google Scholar 

  3. Kadkol, S.S., Brody, J.R., Epstein, J.I., Kuhajda, F.P. & Pasternack, G.R. Novel nuclear phosphoprotein pp32 is highly expressed in intermediate- and high-grade prostate cancer. The Prostate 34, 231–237 (1998).

    Article  CAS  Google Scholar 

  4. Chen, T.H. et al. Structure of pp32, an acidic nuclear protein which inhibits oncogene-induced formation of transformed foci. Mol. Biol. Cell 7, 2045–2056 (1996).

    Article  CAS  Google Scholar 

  5. Malek, S.N., Katumuluwa, A.I. & Pasternack, G.R. Identification and preliminary characterization of two related proliferation-associated nuclear phosphoproteins. J. Biol. Chem. 265, 13400–13409 (1990).

    CAS  PubMed  Google Scholar 

  6. Walensky, L.D., Coffey, D.S., Chen, T.H., Wu, T.C. & Pasternack GR. A novel M(r) 32,000 nuclear phosphoprotein is selectively expressed in cells competent for self-renewal. Cancer Res. 53, 4720–4726 (1993).

    CAS  PubMed  Google Scholar 

  7. Land, H., Parada L.F. & Weinberg, R.A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 304, 596–602 (1993).

    Article  Google Scholar 

  8. Smith TF and Waterman M. Identification of common molecular subsequences. J. Mol. Biol. 147, 195– 197 (1981).

    Article  CAS  Google Scholar 

  9. Vaesen, M. et al. Purification and characterization of two putative HLA class II associated proteins: PHAPI and PHAPII. Biol. Chem. 375, 113–126 (1994).

    CAS  Google Scholar 

  10. Fink, T.M., Vaesen, M., Kratzin, H.D., Lichter, P. & Zimmer, M. Localization of the gene encoding the putative human HLA class II-associated protein (PHAPI) to chromosome 15q22.3-q23 by fluorescence in situ hybridization. Genomics 29, 309–310 (1995).

    Article  CAS  Google Scholar 

  11. Li, M., Makkinje, A. & Damuni, Z. Molecular Identification of I1PP2A, a novel potent heat-stable inhibitor protein of protein phosphatase 2A. Biochemistry 35, 6998–7002 (1996).

    Article  CAS  Google Scholar 

  12. Ulitzur, N., Rancano, C. & Pfeffer, S.R. Biochemical characterization of mapmodulin, a protein that binds microtubule-associated proteins. J. Biol. Chem. 272, 30577–30582 (1997).

    Article  CAS  Google Scholar 

  13. Matsuoka, K. et al. A nuclear factor containing the leucine-rich repeats expressed in murine cerebellar neurons. Proc. Natl. Acad. Sci. USA 91, 9670–9674 (1994).

    Article  CAS  Google Scholar 

  14. Mencinger, M., Panagopoulos, I., Contreras, J.A., Mitelman, F. & Aman, P. Expression analysis and chromosomal mapping of a novel human gene, APRIL, encoding an acidic protein rich in leucines. Biochim. Biophys. Acta 1395, 176– 180 (1998).

    Article  CAS  Google Scholar 

  15. Drwinga, H.L., Toji, L.H., Kim, C.H., Greene, A.E. & Mulivor, R.A. NIGMS human/rodent somatic cell hybrid mapping panels 1 and 2. Genomics 16, 311– 314 (1993).

    Article  CAS  Google Scholar 

  16. Cattoretti, G. et al. Antigen unmasking on formalin-fixed, paraffin-embedded tissue sections. J. Pathol. 171, 83– 98 (1993).

    Article  CAS  Google Scholar 

  17. Gusev, Y. et al. pp32 overexpression induces nuclear pleomorphism in rat prostatic carcinoma cells. Cell Prolif. 29, 643– 653 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank D. Coffey, C.V. Dang, T.J. Kelly Jr., S. Kern, A. Owens Jr., D. Pardoll, H. Shin and S. Sisodia for reading the manuscript, G.S. Bova for providing the paired tissue samples from human prostate cancer patients, and R. Ashworth of The Johns Hopkins DNA Analysis Facility for automated sequencing. This work was supported by USPHS Grant RO1 CA 54404. In accordance with institutional policies, we wish to disclose the following information. G.R.P. is an inventor on US Patents 5756676, 5734022, and 5726018, which encompass the antecedent and present technology described in this manuscript. G.R.P., S.S.K. and J.R.B. are inventors on a pending US Patent application related to the present technology. There is no current licensee or other financial interest for the aforementioned technology.

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Authors and Affiliations

  1. The Division of Molecular Pathology, Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, 21205, Maryland, USA

    Shrihari S. Kadkol, Jonathan R. Brody, Jining Bai & Gary R. Pasternack

  2. Department of Neuroscience, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, 21205, Maryland, USA

    Jonathan Pevsner

  3. Department of Neurology, The Kennedy Krieger Institute, Baltimore, 21205, Maryland, USA

    Jonathan Pevsner

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  1. Shrihari S. Kadkol
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  4. Jining Bai
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Correspondence to Gary R. Pasternack.

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Kadkol, S., Brody, J., Pevsner, J. et al. Modulation of oncogenic potential by alternative gene use in human prostate cancer. Nat Med 5, 275–279 (1999). https://doi.org/10.1038/6488

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