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Fibroblast growth factor-2 and TPA enhance prostate-cancer-cell proliferation and activate members of the Ras and PKC

M Hrzenjak1, S A Shain

  • 1Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, 78284-7836, USA.

Receptors & Signal Transduction
|January 1, 1997
PubMed

Insights

Fibroblast growth factor-2 (FGF-2) and 12-O-tetradecanoylphorbol 12-acetate (TPA) regulate prostate cancer cell proliferation by modulating protein kinase C (PKC) and ras signaling pathways. FGF-2 and TPA independently and together influence cell doubling time.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Signaling

Background:

  • Prostate cancer cell proliferation is influenced by growth factors and signaling molecules.
  • Fibroblast growth factor (FGF) family members play roles in cell growth and differentiation.
  • Understanding the specific roles of FGF-1 and FGF-2 in prostate cancer is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the effects of FGF-2 and 12-O-tetradecanoylphorbol 12-acetate (TPA) on rat prostate cancer cell proliferation.
  • To elucidate the signaling pathways, including protein kinase C (PKC) and ras, involved in FGF-2 and TPA-mediated cell growth modulation.
  • To analyze the differential effects of FGF-1 and FGF-2 knockdown on prostate cancer cell response to FGF-2 and TPA stimulation.

Main Methods:

  • Generation of stable transfectants with antisense-FGF-1 or antisense-FGF-2 to reduce specific FGF protein levels.
  • Measurement of cell doubling time in response to FGF-2 and/or TPA treatment.
  • Assessment of PKC isozyme activation (PKCalpha, PKCepsilon, PKCdelta) via Western blot analysis of cellular fractions.
  • Evaluation of Shc protein phosphorylation as an indicator of ras signaling activation.

Main Results:

  • Antisense-FGF-2 transfectants exhibited significantly increased doubling times, which were reduced by FGF-2 and TPA.
  • Antisense-FGF-1 transfectants also showed increased doubling times, with significant reduction upon combined FGF-2 and TPA treatment, more so than individual treatments.
  • FGF-2 rapidly activated PKCalpha and PKCepsilon, while TPA activated all three PKC isozymes; both treatments led to prolonged PKC activation.
  • FGF-2 induced rapid phosphorylation of Shc, a key component of ras signaling.

Conclusions:

  • FGF-2 and TPA independently and synergistically modulate rat prostate cancer cell proliferation.
  • The observed effects are mediated through signaling pathways involving PKC activation and ras signaling.
  • Targeting FGF-2, TPA, PKC, or ras pathways may offer therapeutic strategies for prostate cancer.

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