Regulation of c-met expression in B16 murine melanoma cells by melanocyte stimulating hormone

1999 ◽  
Vol 112 (5) ◽  
pp. 623-630
Author(s):  
D. Rusciano ◽  
P. Lorenzoni ◽  
M.M. Burger

B16 murine melanoma cells selected in vivo for enhanced liver metastatic ability (B16-LS9) show on the one hand an increased expression and constitutive activation of the proto-oncogene c-met (the receptor for hepatocyte growth factor/scatter factor), and on the other hand a more differentiated phenotype, when compared to the parental cell line, B16-F1. Following this observation, we have tried to establish whether there is a direct relationship between differentiation and c-met expression in B16 melanoma cells. Treatment of these cells with differentiating agents indicated that c-met expression was strongly induced by melanocyte stimulating hormone, while retinoic acid had almost no influence. c-met induction was triggered by engagement of the melanocortin receptor, cAMP elevation and PKA/PKC(α) activation, as respectively shown by the effects of ACTH, cAMP elevating agents and specific PK inhibitors. Regulation of c-met expression via the melanocortin receptor and cAMP raises the intriguing possibility that autocrine and/or paracrine mechanisms acting in vivo on this circuit might influence (through c-met expression and activation) the metastatic behavior of these tumor cells, which we have shown to be dependent on their c-met expression.

1995 ◽  
Vol 147 (2) ◽  
pp. R1-R4 ◽  
Author(s):  
G HUNT ◽  
A J THODY

Abstract In animals, the coat-darkening effects of α-melanocyte stimulating hormone (α-MSH) are opposed by agouti protein. Although agouti protein has been shown to be a competitive antagonist of the melanocyte-associated MC-1 melanocortin receptor, the possibility that agouti protein can affect melanogenesis independently of its ability to antagonise melanocortin activity cannot be excluded. This study demonstrates that murine agouti protein causes both a time- and concentration-dependent suppression of melanogenesis in B16 F1 murine melanoma cells. In addition, human agouti protein decreases melanogenesis in cultured human epidermal melanocytes. However, agouti protein has little effect on the ability of α-MSH to stimulate melanogenesis. These observations raise fundamental questions about the mode of action of agouti protein in regulating melanogenesis.


1996 ◽  
Vol 1 (1) ◽  
pp. 4-9 ◽  
Author(s):  
Hee-Young Park ◽  
Barbara A. Gilchrest

Background: Murine melanoma cells such as Cloudman S91 or B16 mouse melanoma cells have been used extensively to study mechanisms involved in pigmentation because these cells have tyrosinase, the key enzyme in pigmentation, and produce pigment. We have observed that serial passaged S91 cells tend to decrease their basal pigment content and to lose their responsiveness to α-melanocyte-stimulating hormone (α-MSH). Objective: Because this reduction of melanogenic capacity is a widely acknowledged but virtually unstudied characteristic of both human and murine melanoma cell lines in culture, we wished to document and quantify the phenomenon. Methods: Commercially attained S91 melanoma cells were serially passaged. Basal pigmentation as well as α-MSH responsiveness and expression of protein kinase C-beta (PKC-β) were assessed. Results: S91 cells progressively lost their basal pigmentation under standardized conventional conditions of culture, from an initial melanin content of 20 ± 4 pg/cell content to 12 ± 5 pg/cell within 70 population doublings (16 passages) and to 4.5 ± 6 pg/cell, a level at or below the detectable level of our melanin assay, by 110 population doublings (28 passages). When responsiveness to α-MSH was assessed, a 6-day treatment with 10−6M α-MSH initially induced the pigment content four-fold from 20 ± 4 to 82 ± 2 pg/cell. In contrast, after 110 population doublings, identical treatment with α-MSH induced pigment content less than two-fold from 4.5 ± 6 to 7.5 ± 2 pg/cell. PKC-β expression was readily detected by immunofluorescence in early passage pigmented cells, but not in late passage nonpigmented cells. Conclusion: These results confirm that while murine melanoma cells are a useful model system for pigmentation studies, it is important to monitor changes in the cells' basal abilities to pigment and to respond to exogenous pigment-inducing factors. They further suggest that factors in the culture environment or the internal milieu of melanoma cells exposed to continuous mitogenic stimulation inhibit melanogenesis. One candidate mechanism is down regulation of PKC-β.


BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Myra O. Villareal ◽  
Yuki Sato ◽  
Kyoko Matsuyama ◽  
Hiroko Isoda

2014 ◽  
Vol 62 (4) ◽  
pp. 251-264 ◽  
Author(s):  
Ting Lei ◽  
Zheng Huang ◽  
Nobuhiko Ohno ◽  
Bao Wu ◽  
Takashi Sakoh ◽  
...  

Clinics ◽  
2013 ◽  
Vol 68 (7) ◽  
pp. 1018-1027 ◽  
Author(s):  
FV Pereira ◽  
DC Arruda ◽  
CR Figueiredo ◽  
MH Massaoka ◽  
AL Matsuo ◽  
...  

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