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Molecular and Cellular Biology of Prostate Cancer pp 15–26Cite as

Mechanism of Growth Regulation of Androgen Responsive Cells

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Abstract

The DDT1MF-2 cell line, which was derived from a leiomyosarcoma of the hamster ductus deferens, provides an excellent model for the study of androgen responsive cell growth. In this report, we describe serum-free conditions for the maintenance of DDT1MF-2 cells and demonstrate their high sensitivity to steroids and competence factors. Subclones of DDT1MF-2 cells exhibited a range of androgen stimulated growth from highly responsive to totally androgen insensitive. All subclones of DDT1MF-2 cell lines which are non-androgen responsive and grow rapidly in the absence of any exogenous factors are growth inhibited by triamcinolone acetonide treatment. A plasmid containing an androgen response element linked to a chloroamphenical acetyl transferase reporter gene was activated by androgens when it was transfected into subclones that exhibited no androgen dependent growth response. This demonstrates that androgen receptors are biologically active in the non-responsive clones. The doubling time of a highly androgen responsive clone was reduced two-fold by treatment with androgens. The same increase in proliferation rate occurred when testosterone was substituted by acidic FGF, basic FGF, or by PDGF. The increased rate of cell proliferation was completely blocked by treatment with the glucocorticoid triamcinolone acetonide. The effects of androgens and competence factors was also mimicked by the addition of agents which increased intracellular cAMP, such as forskolin, cholera toxin, or beta agonists. Administration of either dibutyryl or 8-bromo cAMP also stimulated cell proliferation. Overall, the DDT1MF-2 cell growth experiments, which were carried out under serum-free defined conditions, illustrate the plasticity of tumor cells and explain how cells which are dependent upon androgens for growth can use alternative survival pathways folJowing androgen ablation. In the absence of androgens, the cells proliferated in response to FGFs, PDGF, or any factor which increased intracellular cAMP levels. Since glucocorticoids inhibit growth of both androgen responsive and non-androgen responsive clones and block the alternative growth pathways, an understanding of this antagonism will provide important targets for the control of both hormone responsive and autonomous tumor growth.

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Author information

Authors and Affiliations

  1. Department of Growth Biochemistry & Physiology, Merck Sharp & Dohme Research Laboratories, P.O. Box 2000, Rahway, New Jersey, 07065, USA

    Roy G. Smith

  2. Scott Department of Urology, USA

    Roy G. Smith & Dolores J. Lamb

  3. Department of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

    Roy G. Smith & Dolores J. Lamb

  4. Alton Jones Cell Science Center, Lake Placid, New York, 12946, USA

    Steve E. Harris

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  1. Roy G. Smith
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Editor information

Editors and Affiliations

  1. Office of Scientific Administration, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    James P. Karr Ph.D. (Chief) (Chief)

  2. The Johns Hopkins Hospital and University, Marburg Building, 600 North Wolfe Street, Baltimore, MD, 21205, USA

    Donald S. Coffey Ph.D. (Professor of Urology, Oncology and Pharmacology) (Professor of Urology, Oncology and Pharmacology)

  3. Department of Growth Biochemistry and Physiology, Merck, Sharpe and Dohme Research Lab, 126 East Lincoln Avenue, Rahway, NJ, 07065, USA

    Roy G. Smith Ph.D.

  4. Mayo Clinic, Guggenheim-4 200 First Street, SW, Rochester, MN, 55905, USA

    Donald J. Tindall Ph.D. (Professor of Urologic Research) (Professor of Urologic Research)

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© 1991 Springer Science+Business Media New York

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Smith, R.G., Harris, S.E., Lamb, D.J. (1991). Mechanism of Growth Regulation of Androgen Responsive Cells. In: Karr, J.P., Coffey, D.S., Smith, R.G., Tindall, D.J. (eds) Molecular and Cellular Biology of Prostate Cancer. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3704-5_2

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  • DOI: https://doi.org/10.1007/978-1-4615-3704-5_2

  • Publisher Name: Springer, Boston, MA

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  • Online ISBN: 978-1-4615-3704-5

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