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Malignant melanoma and melanocortin 1 receptor

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Abstract

The conventional chemotherapeutic treatment of malignant melanoma still remains poorly efficient in most cases. Thus the use of specific features of these tumors for development of new therapeutic modalities is highly needed. Melanocortin 1 receptor (MC1R) overexpression on the cell surface of the vast majority of human melanomas, making MC1R a valuable marker of these tumors, is one of these features. Naturally, MC1R plays a key role in skin protection against damaging ultraviolet radiation by regulating eumelanin production. MC1R activation is involved in regulation of melanocyte cell division. This article reviews the peculiarities of regulation and expression of MC1R, melanocytes, and melanoma cells, along with the possible connection of MC1R with signaling pathways regulating proliferation of tumor cells. MC1R is a cell surface endocytic receptor, thus considered perspective for diagnostics and targeted drug delivery. A number of new therapeutic approaches that utilize MC1R, including endoradiotherapy with Auger electron and α- and β-particle emitters, photodynamic therapy, and gene therapy are now being developed.

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Abbreviations

ACTH:

adrenocorticotropin

AGRP:

agouti-related protein

α-MSH:

α-melanocyte-stimulating hormone

ARRB1:

arrestin-beta-1

ARRB2:

arrestin-beta-2

ASIP:

agouti signal protein

Bcl-2:

apoptosis regulator from B-cell lymphoma 2

BD3:

β-defensin 3

BRAF:

v-Raf murine sarcoma viral oncogene homolog B1

CDKN2A:

cyclin-dependent kinase inhibitor 2A

CRE:

cAMP-responsive element

CREB:

cAMP-responsive element-binding protein

ERK:

extracellular signal-regulated kinases

GPCR:

G-protein coupled receptors

GRK:

GPCR kinase

I-κB:

nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor

LET:

linear energy transfer

MAPK:

mitogen-activated protein kinases

MC1R:

melanocortin 1 receptor

MGRN1:

mahogunin RING finger-1 (ubiquitin E3 ligase with RING-domain)

MITF:

microphthalmia transcription factor

MRAP:

melanocortin-2-receptor accessory protein

mTor:

mammalian target of rapamycin

NEDD9:

neural precursor cell expressed, developmentally down-regulated 9

NF-κB:

nuclear factor kappa-light-chain-enhancer of activated B cells

NIS:

Na-I symporter

PKA:

protein kinase A

RING:

real interesting new gene

Sdc2:

syndecane-2

TUBB3:

β-III-tubulin

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Authors and Affiliations

  1. Institute of Gene Biology, Russian Academy of Sciences, ul. Vavilova 34/5, 199334, Moscow, Russia

    A. A. Rosenkranz, T. A. Slastnikova, M. O. Durymanov & A. S. Sobolev

  2. Faculty of Biology, Lomonosov Moscow State University, Leninsky Gory 1-12, 119234, Moscow, Russia

    A. A. Rosenkranz, M. O. Durymanov & A. S. Sobolev

  3. Targeted Delivery of Pharmaceuticals “Translek” LLC, ul. Vavilova 34/5, 199334, Moscow, Russia

    A. A. Rosenkranz & A. S. Sobolev

Authors
  1. A. A. Rosenkranz
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  2. T. A. Slastnikova
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  3. M. O. Durymanov
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  4. A. S. Sobolev
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Correspondence to A. A. Rosenkranz.

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Published in Russian in Biokhimiya, 2013, Vol. 78, No. 11, pp. 1564–1575.

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Rosenkranz, A.A., Slastnikova, T.A., Durymanov, M.O. et al. Malignant melanoma and melanocortin 1 receptor. Biochemistry Moscow 78, 1228–1237 (2013). https://doi.org/10.1134/S0006297913110035

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