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Androgen receptor expression in primary prostate cancers of lobund-wistar rats and in tumor-derived cell lines

  • Growth, Differentiation, And Senescence
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Summary

Prostate tumors were induced in Lobund-Wistar rats by treatment with N-methyl-N-nitrosourea (MNU) and testosterone propionate (TP). Androgen receptor (AR) expression was confirmed in 16 (100%) of the primary prostate cancers, with strong uniform staining in well-differentiated tumors and more variable AR immunoreactivity in poorly differentiated tumors. Epithelial cell lines were established from nine of the tumors. At early passages, four of the tumor cell lines tested were strongly immunoreactive for AR; however, only two of the cell lines, E2(A) and F2, have remained AR-positive. These cell lines specifically bind 3H-DHT at 40 and 19 fmol/mg protein, respectively, and express a 110 kDa AR immunoreactive protein. Proliferation in in vitro culture of both E2(A) and F2 cells was increased in the presence of 5α-dihydrotestosterone (DHT). The antiandrogen, hydroxyflutamide was able to prevent the DHT-induced growth of E2(A) but not F2 cells. Furthermore, hydroxyflutamide alone increased proliferation of F2 cells, suggesting that the androgen signalling pathway in this cell line may be abnormal. Tumorigenicity of the AR-expressing and nonexpressing cell lines was confirmed by xenograft formation following subcutaneous inoculation into intact male nude mice. In summary, carcinogen-induced prostate tumors of Lobund-Wistar rats express AR and two of nine cell lines derived from the tumors express AR. Further evaluation of AR structure in primary prostate tumors forming spontaneously or following MNU and TP induction will determine whether, as in human prostate cancers, disease progression in Lobund-Wistar rats is associated with mutations in the AR gene.

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Author notes

  1. Jacqueline M. Bentel

    Present address: Department of Pathology, Royal Perth Hospital, Wellington Street, 6000, Perth, WA, Australia

Authors and Affiliations

  1. Urological Research Centre, QEII Medical Centre, 6009, Nedlands, Western Australia

    Jacqueline M. Bentel

  2. Flinders Cancer Centre, Flinders Medical Centre, 5042, Bedford Park, South Australia

    Marie A. Pickering & Wayne D. Tilley

  3. University of Notre Dame Lobund Laboratory, 46556, Notre Dame, Indiana, USA

    Morris Pollard

  4. Prince Henry’s Institute for Medical Research, 3168, Clayton, Victoria

    Judith A. Clements

Authors
  1. Jacqueline M. Bentel
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  2. Marie A. Pickering
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  4. Judith A. Clements
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  5. Wayne D. Tilley
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Bentel, J.M., Pickering, M.A., Pollard, M. et al. Androgen receptor expression in primary prostate cancers of lobund-wistar rats and in tumor-derived cell lines. In Vitro Cell.Dev.Biol.-Animal 35, 655–662 (1999). https://doi.org/10.1007/s11626-999-0106-5

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  • DOI: https://doi.org/10.1007/s11626-999-0106-5

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