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Autocrine regulation of growth: I. Glucocorticoid inhibition is overcome by exogenous platelet derived growth factor

A J Syms, J S Norris, R G Smith

    Biochemical and Biophysical Research Communications
    |July 18, 1984
    PubMed

    Insights

    Platelet-derived growth factor (PDGF) drives proliferation in DDT1MF-2 cells. Glucocorticoids inhibit this growth and cell cycle progression, but PDGF can override the arrest independently of androgen receptor levels.

    Area of Science:

    • Oncology
    • Cell Biology
    • Endocrinology

    Background:

    • The ductus deferens smooth muscle tumor cell line (DDT1MF-2) is a model for studying cell proliferation.
    • Platelet-derived growth factor (PDGF) is a potent mitogen involved in cell growth regulation.
    • Hormonal influences, including androgens and glucocorticoids, play a role in regulating cell proliferation.

    Purpose of the Study:

    • To investigate the role of platelet-derived growth factor (PDGF) in the autocrine regulation of DDT1MF-2 cell proliferation.
    • To elucidate the mechanisms by which androgens and glucocorticoids affect DDT1MF-2 cell proliferation and androgen receptor levels.
    • To determine the interplay between PDGF, glucocorticoids, and androgen receptor signaling in DDT1MF-2 cells.

    Main Methods:

    • Analysis of c-sis protooncogene mRNA transcripts and PDGF protein expression in DDT1MF-2 cells.
    • Assessment of cell proliferation rates under various hormonal and growth factor treatments.
    • Cell cycle analysis to determine the effects of glucocorticoids and PDGF on cell cycle progression.
    • Measurement of androgen receptor levels in response to different treatments.

    Main Results:

    • DDT1MF-2 cells express c-sis protooncogene mRNA and secrete PDGF, suggesting autocrine PDGF signaling.
    • Androgens stimulate DDT1MF-2 cell proliferation and increase androgen receptor levels.
    • Glucocorticoids inhibit proliferation, arrest cells in G1 phase, and decrease androgen receptor levels.
    • Exogenous PDGF addition overcomes glucocorticoid-induced cell cycle arrest but does not affect the suppression of androgen receptor concentration.

    Conclusions:

    • PDGF is implicated in the autocrine regulation of DDT1MF-2 cell proliferation.
    • Glucocorticoids regulate DDT1MF-2 cell proliferation via modulation of PDGF expression, independent of their effects on androgen receptor levels.
    • This study reveals a complex interplay between growth factors and steroid hormones in regulating tumor cell growth.

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