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Variable Effects of Growth Factors on Developmental Gene Expression in Pancreatic Cancer Cells

D A Gnatenko1, E P Kopantzev2, E D Sverdlov2

  • 1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia. gnatenkodmitrij@gmail.com.

Doklady. Biochemistry and Biophysics
|September 1, 2018
PubMed

Insights

Growth factors like EGF and FGFs alter key pancreatic development genes (SOX9, HNF3b, GATA-4, GATA-6, HES1) in pancreatic cancer cells. This impacts embryonic development regulators, with some genes having opposing effects within the same cell line.

Area of Science:

  • Oncology
  • Developmental Biology
  • Molecular Biology

Background:

  • Pancreatic cancer cell lines (BxPC-3, Panc-1, MIA PaCA-2) are crucial models for studying cancer progression.
  • Understanding the molecular mechanisms driving pancreatic cancer is essential for developing targeted therapies.
  • Growth factors play significant roles in both normal development and cancer, but their specific impact on pancreatic cancer cell gene expression requires further elucidation.

Purpose of the Study:

  • To investigate the effects of various growth factors on the expression of master regulatory genes involved in pancreatic development within pancreatic cancer cell lines.
  • To determine how these changes in master gene expression influence the profile of transcription factors and embryonic development regulators.
  • To explore potential differential or opposing effects of growth factors from the same family on gene expression within these cancer cells.

Main Methods:

  • Treatment of pancreatic cancer cell lines (BxPC-3, Panc-1, MIA PaCA-2) with specific growth factors: Epidermal Growth Factor (EGF), Hepatocyte Growth Factor (HGF), Fibroblast Growth Factors (FGF-1, FGF-2, FGF-7, FGF-10).
  • Analysis of changes in the expression of key pancreatic development master genes: SOX9, HNF3b, GATA-4, GATA-6, and HES1.
  • Assessment of the subsequent alterations in the expression profiles of transcription factors and regulators of embryonic development.

Main Results:

  • Growth factor stimulation led to significant alterations in the expression of SOX9, HNF3b, GATA-4, GATA-6, and HES1 in pancreatic cancer cells.
  • These changes in master gene expression subsequently modified the expression of critical transcription factors involved in embryonic development.
  • Notably, growth factors within the same family (e.g., FGFs) exhibited contrasting effects, either suppressing or enhancing the expression of specific transcriptional regulators in the same cell line.

Conclusions:

  • Growth factor signaling pathways profoundly influence the expression of developmental genes in pancreatic cancer cells.
  • The observed alterations in master gene expression have downstream consequences on the regulatory network of embryonic development, potentially impacting cancer cell behavior.
  • The differential and sometimes opposing effects of related growth factors highlight the complexity of signaling networks in pancreatic cancer and suggest potential therapeutic targets.

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