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Regulation of melanin synthesis by the TGF-β family in B16 melanoma cells

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Abstract

Effects of representative members of the transforming growth factor-β (TGF-β) family, TGF-β1, activin A and BMP-2, on melanin content and expression of pigment-producing enzymes were examined in B16 melanoma cells. Treatment with TGF-β1 or activin A but not with BMP-2 significantly decreased melanin content and expression of Tyrosinase and Tyrp-1, suggesting an inhibitory effect of TGF-β1 and activin A on melanin synthesis. TGF-β1 completely inhibited melanin synthesis induced by α-melanin stimulating hormone (α-MSH), whereas activin A only slightly did. As compared with parental B16 cells, the inhibitory effects of TGF-β1 and activin A on melanin content were relative smaller in B16 F10 cells, a subline of B16 cells that contain more pigment. The present study indicates that in addition to TGF-β, activin negatively regulates melanogenesis in the absence of α-MSH, but that the activity in the presence of α-MSH was slightly different between TGF-β and activin.

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References

  1. del Marmol V, Beermann F (1996) Tyrosinase and related proteins in mammalian pigmentation. FEBS Lett 381:165–168

    Article  PubMed  Google Scholar 

  2. Slominski A, Tobin DJ, Shibahara S, Wortsman J (2004) Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev 84:1155–1228

    Article  PubMed  CAS  Google Scholar 

  3. Costin GE, Hearing VJ (2007) Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J 21:976–994

    Article  PubMed  CAS  Google Scholar 

  4. Kadekaro AL, Wakamatsu K, Ito S, Abdel-Malek ZA (2006) Cutaneous photoprotection and melanoma susceptibility: reaching beyond melanin content to the frontiers of DNA repair. Front Biosci 11:2157–2173

    Article  PubMed  CAS  Google Scholar 

  5. Schilling SH, Hjelmeland AB, Rich JN, Wang X-F (2007) TGF-β: a multipotential cytokine. In: Derynck R, Miyazono K (eds) The TGF-β family. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 45–77

    Google Scholar 

  6. Feng XH, Derynck R (2005) Specificity and versatility in TGF-β signaling through Smads. Annu Rev Cell Dev Biol 21:659–693

    Article  PubMed  CAS  Google Scholar 

  7. Massagué J, Seoane J, Wotton D (2005) Smad transcription factors. Genes Dev 19:2783–2810

    Article  PubMed  Google Scholar 

  8. Martínez-Esparza M, Jiménez-Cervantes C, Beermann F, Aparicio P, Lozano JA, García-Borrón JC (1997) Transforming growth factor-β1 inhibits basal melanogenesis in B16/F10 mouse melanoma cells by increasing the rate of degradation of tyrosinase and tyrosinase-related protein-1. J Biol Chem 272:3967–3972

    Article  PubMed  Google Scholar 

  9. Martínez-Esparza M, Solano F, García-Borrón JC (1999) Independent regulation of tyrosinase by the hypopigmenting cytokines TGFβ1 and TNFα and the melanogenic hormone α-MSH in B16 mouse melanocytes. Cell Mol Biol (Noisy-le-grand) 45:991–1000

    Google Scholar 

  10. Kim DS, Park SH, Park KC (2004) Transforming growth factor-β1 decreases melanin synthesis via delayed extracellular signal-regulated kinase activation. Int J Biochem Cell Biol 36:1482–1491

    PubMed  CAS  Google Scholar 

  11. Martínez-Esparza M, Ferrer C, Castells MT, García-Borrón JC, Zuasti A (2001) Transforming growth factor β1 mediates hypopigmentation of B16 mouse melanoma cells by inhibition of melanin formation and melanosome maturation. Int J Biochem Cell Biol 33:971–983

    Article  PubMed  Google Scholar 

  12. Murakami M, Ikeda T, Saito T, Ogawa K, Nishino Y, Nakaya K, Funaba M (2006) Transcriptional regulation of plasminogen activator inhibitor-1 by transforming growth factor-β, activin A and microphthalmia-associated transcription factor. Cell Signal 18:256–265

    Article  PubMed  CAS  Google Scholar 

  13. Funaba M, Ikeda T, Murakami M, Ogawa K, Tsuchida K, Sugino H, Abe M (2003) Transcriptional activation of mouse mast cell protease-7 by activin and transforming growth factor-β is inhibited by microphthalmia-associated transcription factor. J Biol Chem 278:52032–52041

    Article  PubMed  CAS  Google Scholar 

  14. Heredia A, Villena J, Romarís M, Molist A, Bassols A (1996) The effect of TGF-β1 on cell proliferation and proteoglycan production in human melanoma cells depends on the degree of cell differentiation. Cancer Lett 109:39–47

    Article  PubMed  CAS  Google Scholar 

  15. Bilodeau ML, Greulich JD, Hullinger RL, Bertolotto C, Ballotti R, Andrisani OM (2001) BMP-2 stimulates tyrosinase gene expression and melanogenesis in differentiated melanocytes. Pigment Cell Res 14:328–336

    Article  PubMed  CAS  Google Scholar 

  16. Nakamura K, Yoshikawa N, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo M (2002) Characterization of mouse melanoma cell lines by their mortal malignancy using an experimental metastatic model. Life Sci 70:791–798

    Article  PubMed  CAS  Google Scholar 

  17. Yaar M, Wu C, Park HY, Panova I, Schutz G, Gilchrest BA (2006) Bone morphogenetic protein-4, a novel modulator of melanogenesis. J Biol Chem 281:25307–25314

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by Kakenhi (17580262 and 18580299) from the Japan Society for the Promotion of Science, and by grants for Graduate Schools from The Foundation for Japanese Private School Promotion, and by The Science Research Promotion Fund from The Promotion and Mutual Aid Corporation for Private Schools of Japan.

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Correspondence to Masayuki Funaba.

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Murakami, M., Matsuzaki, F. & Funaba, M. Regulation of melanin synthesis by the TGF-β family in B16 melanoma cells. Mol Biol Rep 36, 1247–1250 (2009). https://doi.org/10.1007/s11033-008-9304-6

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  • DOI: https://doi.org/10.1007/s11033-008-9304-6

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