title: Diethylstilbestrol enhances melanogenesis via cAMP-PKA-mediating up-regulation of tyrosinase and MITF in mouse B16 melanoma cells.
abstract: BACKGROUND
  It is well known that melanin synthesis in melanoma cells is controlled by melanogenic enzymes, which regulate the cAMP-PKA signaling pathway. Estrogen was previously reported to upregulate melanogenesis that is associated with human skin pigmentation.
  
  
  OBJECTIVE
  To investigate the influence and mechanism of diethylstilbestrol (DES) on melanogenesis in mouse B16 melanoma cells.
  
  
  METHODS
  The effects of diethylstilbestrol on cell viability, melanin content, tyrosinase activity, cAMP level, expression of the tyrosinase family and microphthalmia related transcription factor (MITF) were measured in B16 melanoma. Estrogen receptor (ER) expression were detected in B16 melanoma and A375 melanoma. Diethylstilbestrol-induced melanin synthesis were evaluated in the presence and absence of H89 (a PKA-specific inhibitor) and ICI182, 780 (a pure ER antagonist). Tyrosinase activity, the mRNA levels of tyrosinase and MITF were evaluated in the presence and absence of H89.
  
  
  RESULTS
  In B16 cells, diethylstilbestrol increased cell proliferation, melanin synthesis, tyrosinase activity and expression of the tyrosinase family and MITF. ER expression have not difference in human and mouse melanoma. When ER were inhibited by ICI182, 780, DES-induced melanogenesis was significantly reduced. Diethylstilbestrol enhanced the level of cAMP. The upregulation of melanin content and tyrosinase activity stimulated by diethylstilbestrol was significantly attenuated in the presence of H89. Further, diethylstilbestrol-induced upregulation of tyrosinase and MITF were significantly attenuated when the PKA pathway was blocked.
  
  
  CONCLUSIONS
  Diethylstilbestrol can enhance melanin synthesis in melanoma cells. This effect is associated with activation of the cAMP-PKA pathway and upregulation of expression and activity of the melanogenesis-related enzyme tyrosinase and MITF.
authors: Department of Dermatology, XiangYa Hospital, Central South University, Changsha, Hunan, China.
authors: Dan
authors: D
authors: Jian
authors: Dejian
authors: D
authors: Jiang
authors: Juan
authors: J
authors: Su
authors: Wei
authors: W
authors: Chen
authors: Xinglin
authors: X
authors: Hu
authors: Yehong
authors: Y
authors: Kuang
authors: Hongfu
authors: H
authors: Xie
authors: Ji
authors: J
authors: Li
authors: Xiang
authors: X
authors: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D007546:Isoquinolines; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D004054:Diethylstilbestrol; D000242:Cyclic AMP; D014442:Monophenol Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide