Determination of the antitumor activity of the L21R peptide derived from the Brn-2 transcription factor in murine melanoma B16F10-Nex2

Abstract

Melanocytes are located in the basal layer of the epidermis, hair follicles, uveal eye tract and cochlea. Melanocytes are cells that produce of melanin, protein responsible for color to the skin, eye color and hair. Melanoma is originated when melanocytes undergo malignant transformation. This tumor cell results from the accumulation of genetic mutations able of modifying the expression of genes encoding proteins intrinsic to the regulatory pathways of protein molecules responsible for controlling cell proliferation and adhesion. In addition, changes in cell signaling pathways are also important in the malignant transformation process, as well as changes in levels of transcription factors. Brn-2 protein is associated with the normal development of melanocytic lineage, and when overexpressed can activate signals for abnormal growth as in malignant melanoma, in addition to inducing cell proliferation and invasion. Gene expression of the Brn-2 transcription factor is regulated by three signaling pathways: Wnt / ²-catenin, MAPK and PI3K / AKT. Studies show that peptides derived from transcription factors induce cell death. Peptides are particularly reactive molecules produced by several species. They exhibit high affinity and specificity in target tissues, in addition to low toxicity. Some mechanisms of cell death induced by peptide are: apoptosis, necrosis and senescence. The L21R peptide, derived from the Brn-2 transcription factor, could interfere with both the mechanisms of cell death and tumor growth factors by competing with the Brn-2 binding site in DNA. (AU)