Mechanisms of differentiation in melanoma cells and melanocytes.

Bennett, Dorothy C.

doi:10.1289/ehp.898049

Cited by 39 publications

(21 citation statements)

References 94 publications

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“…In contrast to the observations in development, pigmented primary melanocytes and melanoma cells retain the potential for division in culture (Bennett, 1983;Bennett, 1989;Bennett et al, 1985). Time-lapse imaging of melanoma cell culture have captured cell division of pigmented melanoma cells in mitosis, and normal diploid pigmented human melanocytes can divide as quickly as unpigmented cells.…”

Section: Introductionmentioning

confidence: 87%

Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf

Taylor

Lister

Zeng³

et al. 2011

Development

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SUMMARYCoordination of cell proliferation and differentiation is crucial for tissue formation, repair and regeneration. Some tissues, such as skin and blood, depend on differentiation of a pluripotent stem cell population, whereas others depend on the division of differentiated cells. In development and in the hair follicle, pigmented melanocytes are derived from undifferentiated precursor cells or stem cells. However, differentiated melanocytes may also have proliferative capacity in animals, and the potential for differentiated melanocyte cell division in development and regeneration remains largely unexplored. Here, we use time-lapse imaging of the developing zebrafish to show that while most melanocytes arise from undifferentiated precursor cells, an unexpected subpopulation of differentiated melanocytes arises by cell division. Depletion of the overall melanocyte population triggers a regeneration phase in which differentiated melanocyte division is significantly enhanced, particularly in young differentiated melanocytes. Additionally, we find reduced levels of Mitf activity using an mitfa temperature-sensitive line results in a dramatic increase in differentiated melanocyte cell division. This supports models that in addition to promoting differentiation, Mitf also promotes withdrawal from the cell cycle. We suggest differentiated cell division is relevant to melanoma progression because the human melanoma mutation MITF 4T⌬2B promotes increased and serial differentiated melanocyte division in zebrafish. These results reveal a novel pathway of differentiated melanocyte division in vivo, and that Mitf activity is essential for maintaining cell cycle arrest in differentiated melanocytes.

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Section: Introductionmentioning

confidence: 87%

Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf

Taylor

Lister

Zeng³

et al. 2011

Development

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“…Stimulation of pigment cell differentiation by cAMP agonists is a long-studied topic (e.g. Wong and Pawelek, 1975;Halaban et al, 1983;Bennett, 1989;Haddad et al, 1999;Busca`and Ballotti, 2000). Pathways include both stimulation of transcription of specialized melanocytic proteins (for reviews, see Busca`and Ballotti, 2000;Goding, 2000) and post-translational activation of the key melanosomal enzyme tyrosinase (Wong and Pawelek, 1975).…”

Section: Senescence In Cultured Human Melanocytesmentioning

confidence: 99%

Human melanocyte senescence and melanoma susceptibility genes

2003

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The molecular mechanisms and biology of cellular senescence in human melanocytes are discussed, including similarities to and differences from senescence in fibroblasts and other cell lineages. Special reference is made to the fact that the known melanoma susceptibility genes in the human, Inhibitor A of [cyclin-dependent] kinase 4-alternative reading frame (INK4A-ARF) and cyclindependent kinase 4, are involved in the regulation of cellular senescence, and possible reasons why this should be so. Based on the evidence including growth and survival kinetics of human and mouse melanocytes carrying germline deficiencies in the INK4A sequence, it is suggested that an 'M0' or p16/RB-dependent form of senescence may be particularly important in melanocytes. A speculative model is proposed, relating current concepts of early melanoma progression to the processes of cellular senescence and immortalization. This includes the suggestion that moles or nevi are senescent clones of melanocytes.

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“…The prime candidates for studies of melanocyte-specific gene expression are those genes, such as the tyrosinase gene, which maps to the albino locus (2,17,25,47), and the TRP-1 gene, located at the brown locus (5,19), involved in melanogenesis, a process which is unique to melanocytes and which occurs only after differentiation from the nonpigmented precursor, the melanoblast (3). The identification of the transcription factors responsible for the regulation of the tyrosinase and TRP-1 genes 13-Gal and CAT assays.…”

mentioning

confidence: 99%

Positive and negative elements regulate a melanocyte-specific promoter.

Lowings¹,

Yavuzer²,

Goding³

1992

Mol. Cell. Biol.

129

128

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Melanocytes are specialized cells residing in the hair follicles, the eye, and the basal layer of the human epidermis whose primary function is the production of the pigment melanin, giving rise to skin, hair, and eye color. Melanogenesis, a process unique to melanocytes that involves the processing of tyrosine by a number of melanocyte-specific enzymes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), occurs only after differentiation from the melanocyte precursor, the melanoblast. In humans, melanogenesis is inducible by UV irradiation, with melanin being transferred from the melanocyte in the epidermis to the surrounding keratinocytes as protection from UV-induced damage. Excessive exposure to UV, however, is the primary cause of malignant melanoma, an increasingly common and highly aggressive disease. As an initial approach to understanding the regulation of melanocyte differentiation and melanocyte-specific transcription, we have isolated the gene encoding TRP-1 and examined the cis-and trans-acting factors required for cell-type-specific expression. We find that the TRP-1 promoter comprises both positive and negative regulatory elements which confer efficient expression in a TRP-1-expressing, pigmented melanoma cell line but not in NIH 3T3 or JEG3 cells and that a minimal promoter extending between -44 and +107 is sufficient for cell-type-specific expression. Assays for DNA-protein interactions coupled with extensive mutagenesis identified three factors, whose binding correlated with the function of two positive and one negative regulatory element. One of these factors, termed M-box-binding factor 1, binds to an 11-bp motif, the M box, which acts as a positive regulatory element both in TRP-l-expressing and -nonexpressing cell lines, despite being entirely conserved between the melanocyte-specific tyrosinase and TRP-1 promoters. The possible mechanisms underlying melanocyte-specific gene expression are discussed.

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Mechanisms of differentiation in melanoma cells and melanocytes.

Cited by 39 publications

References 94 publications

Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf

Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf

Human melanocyte senescence and melanoma susceptibility genes

Positive and negative elements regulate a melanocyte-specific promoter.

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