Role of retinoid mediated microphthalmia-associated transcription factor (MITF) in melanoma

Abstract

Retinoic acid is the most effective therapeutic drug for the treatment of many types of cancer, including melanoma. All-trans retinoic acid (ATRA) increases the protein level of MITF in melanoma cells within 2 to 4 days (Chan, 2007), indicating that RA induced MITF plays a vital role in its anti-proliferative action. On the contrary, MITF silencing can induce senescence in melanoma cells. These two different roles of the same protein are dependent on a band of threshold level. The expression of MITF below threshold band level results in senescence and above it causes cell differentiation and consequently cell cycle arrest. The anti-proliferative effect of ATRA, mediated by MITF, increases its expression above threshold level and targets other cell cycle regulators to suppress proliferation. This role of RA mediated MITF is elucidated in the present paper showing the internal looping of MITF with other target genes of retinoids to cause differentiation in melanoma cells. The paper presents a novel model of internal looping of genes in double ring resonator form fabricated in MATLAB2008. It is interesting to note that a strong coupling factor of MITF with RA dependent genes reduces proliferation and a weak coupling between these genes increases proliferation, thus reflecting the dual role of the same protein. Key words: Microphthalmia-associated transcription factor, retinoic acid, homeostasis, ring resonator, Simulink