Alterations in the Expression of MHC Class I Glycoproteins by B16BL6 Melanoma Cells Modulate Insulin Receptor-Regulated Signal Transduction and Augments Resistance to Apoptosis

  • Assa-Kunik E
  • Fishman D
  • Kellman-Pressman S
  • et al.
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Abstract

In a variety of malignancies, the immune-escape phenotype is associated, in part, with the inability of tumor cells to properly present their Ags to CTLs due to a deranged expression of MHC class I glycoproteins. However, these molecules were found to possess broader nonimmune functions, including participation in signal transduction and regulation of proliferation, differentiation, and sensitivity to apoptosis-inducing factors; processes, which are characteristically impaired during malignant transformation. We investigated whether the deranged expression of MHC class I expression by tumor cells could affect proper receptor-mediated signal transduction and accentuate their malignant phenotype. The malignant and H-2K murine MHC class I-deficient B16BL6 melanoma cells were characterized by an attenuated capacity to bind insulin due to the retention of corresponding receptor in intracellular stores. The restoration of H-2K expression in these cells, which abrogated their capacity to form tumors in mice, enhanced membrane translocation of the receptor, presumably, by modulating its glycosylation. The addition of insulin to H-2K-expressing melanoma cells cultured in serum-free conditions precluded apoptotic death by up-regulating the activity of protein kinase B (PKB)/Akt. In contrast, the deficiency for H-2K characteristic to the malignant clones was associated with a constitutive high activity of PKB/Akt, which rendered them resistant to apoptosis, induced by deprivation of serum-derived growth factors. The possibility to correct the regulation of PKB/Akt activity by restoration of H-2K expression in B16BL6 melanoma cells may be considered as an attractive approach for cancer therapy, since an aberrant activation of this enzyme is characteristic to resistant malignancies.

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APA

Assa-Kunik, E., Fishman, D., Kellman-Pressman, S., Tsory, S., Elhyany, S., Baharir, O., & Segal, S. (2003). Alterations in the Expression of MHC Class I Glycoproteins by B16BL6 Melanoma Cells Modulate Insulin Receptor-Regulated Signal Transduction and Augments Resistance to Apoptosis. The Journal of Immunology, 171(6), 2945–2952. https://doi.org/10.4049/jimmunol.171.6.2945

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