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Mannose 6-phosphate/insulin-like growth factor II receptor mediates the growth-inhibitory effects of retinoids

J X Kang1, J Bell, R L Beard

  • 1Department of Medicine, Massachusetts General Hospital, Charlestown 02129-2000, USA. kang.jing@mgh.harvard.edu

Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
|September 2, 1999
PubMed

Insights

The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) mediates retinoid-induced growth inhibition and apoptosis, independent of retinoic acid nuclear receptors (RARs). This finding offers insight into retinoid and M6P/IGF2R roles in development and cancer.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Oncology

Background:

  • Retinoids and M6P/IGF2R are crucial in cell growth control during development and cancer.
  • Previous research indicated a biochemical link between retinoic acid (RA) and M6P/IGF2R.

Purpose of the Study:

  • To investigate if M6P/IGF2R mediates the growth-inhibiting effects of RA.
  • To explore the role of M6P/IGF2R in retinoid-induced apoptosis and growth inhibition.

Main Methods:

  • Examined cell growth and apoptosis in cells with varying M6P/IGF2R expression in response to RA and retinoids.
  • Utilized stably transfected mouse P388D1 cells, M6P/IGF2R-deficient cells, and cultured neonatal rat cardiac myocytes.
  • Tested RA effects using RAR antagonist (AGN193109) and RAR agonist (TTNPB).
  • Investigated RA-induced apoptosis in a RA-resistant cancer cell line (HL-60R) with M6P/IGF2R overexpression.

Main Results:

  • RA and M6P/IGF2R-binding retinoids induced apoptosis, growth inhibition, and morphological changes in M6P/IGF2R-overexpressing cells, but not in deficient cells.
  • These RA effects were independent of RARs, as shown by antagonist and agonist studies.
  • Similar retinoid effects were observed in neonatal rat cardiac myocytes.
  • Overexpression of M6P/IGF2R sensitized RA-resistant cancer cells (HL-60R) to RA-induced apoptosis.

Conclusions:

  • M6P/IGF2R plays a significant role in mediating retinoid-induced apoptosis and growth inhibition.
  • The findings suggest a mechanism for retinoid action independent of RARs.
  • This research provides insights into the shared biological roles of RA and M6P/IGF2R in embryonic development and carcinogenesis.

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