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Down-regulation of insulin-like growth factor binding proteins and growth modulation in hepatoma cells by retinoic

D G Kim1, D Y Lee, B H Cho

  • 1Division of GI and Hepatology, Institute for Medical Science, Chonbuk National University Medical School and Hospital, Chonju, Chonbuk, Republic of Korea.

Hepatology (Baltimore, Md.)
|March 30, 1999
PubMed

Insights

All-trans-retinoic acid (RA) affects cell growth by down-regulating insulin-like growth factor binding proteins (IGFBPs) in hepatoma cells. This regulation influences cell proliferation independently of insulin-like growth factors (IGFs).

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • All-trans-retinoic acid (RA) is a derivative of vitamin A with known roles in cell differentiation and growth.
  • Insulin-like growth factor binding proteins (IGFBPs) modulate the bioavailability and activity of insulin-like growth factors (IGFs), influencing cell proliferation.
  • Hepatoma cells are malignant cells originating from the liver, and their growth is often dysregulated.

Purpose of the Study:

  • To investigate the effect of all-trans-retinoic acid (RA) on insulin-like growth factor binding proteins (IGFBPs) in human hepatoma cells.
  • To characterize the role of RA-induced down-regulation of IGFBPs in modulating hepatoma cell growth.
  • To determine whether RA's effects on cell growth are mediated by IGFs or are independent.

Main Methods:

  • Culturing human hepatoma cell lines (Hep 3B, PLC/PRF/5, and Hep G2).
  • Treating cells with all-trans-retinoic acid (RA) and measuring changes in IGFBP levels (specifically IGFBP-1 and IGFBP-3).
  • Assessing cell growth in response to RA, IGFs, and different forms of IGFBPs (phosphorylated and dephosphorylated).

Main Results:

  • RA treatment rapidly decreased IGFBP-3 in Hep 3B cells, leading to time-dependent growth stimulation.
  • RA decreased IGFBP-1 in PLC/PRF/5 and Hep G2 cells, resulting in transient and less prominent growth stimulation.
  • IGFBP-3 inhibited hepatoma cell growth and partially counteracted RA's growth-stimulatory effects; dephosphorylated IGFBP-1 stimulated growth independently of IGF-I.

Conclusions:

  • All-trans-retinoic acid (RA) down-regulates IGFBPs in hepatoma cells, modulating cell growth through an autocrine mechanism independent of IGFs.
  • RA regulates IGFBPs at either the post-transcriptional (Hep 3B, Hep G2) or transcriptional (PLC/PRF/5) level, indicating cell-specific regulation.
  • These findings highlight a novel mechanism by which RA influences hepatoma cell proliferation via IGFBP modulation.

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