Skin cancer prevention

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Skin cancer prevention or, why redheads dont tan
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UV triggers secretion of melanogenic substance by
keratinocytes
Pigment program activation
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UV induces MSH in keratinocytes
Keratinocytes
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Is the melanin pathway rescuable downstream of
MC1R?
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Can topical drug rescue Mc1r in redhead mice?
Protective against sunburn, pyrimidine dimer
formation Protective against UV-carcinogenesis
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Increased melanin protects against sunburning
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Decreased DNA damage in topically-treated skin
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Protection against UV-cancers in cancer-prone
mice
Squamous Cell Ca, Papilloma, Fibrosarcoma
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How does UV trigger POMC/MSH expression in
keratinocytes?
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How does UV induce MSH in melanocytes?
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P53 binds endogenous POMC promoter and is
required for UV induction of POMC
P53 binds endogenous POMC promoter after UV
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P53-/- mice cannot tan
p53 knockouts cannot tan
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Human UV-Irradiated Skin
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P53 mediates post-inflammatory hyperpigmentation-
Many causes, common mediator
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UV stimulation of keratinocytes induces
melanocytes to produce melanin
UV radiation
Keratinocyte
p53
MSH
Melanin
MC1R
Y
MITF
Melanocyte
Cui et al. Cell 2007
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POMC products

• Adrenocorticotrophic Hormone (ACTH)
• Melanocyte Stimulating Hormone (MSH)
• b-endorphin
• others

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POMC products

• Adrenocorticotrophic Hormone (ACTH)
• Melanocyte Stimulating Hormone (MSH)
• b-endorphin
• others

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Collaborators
ACKNOWLEDGEMENTS
Stanley Korsmeyer Martin Mihm Roy King Jonathan
Fletcher Sara Vargas Sridhar Ramaswamy Scott
Granter Todd Golub Jun Song X. Shirley
Liu William Sellers Levi Garraway David
Rimm Aaron Berger Mark Rubin Sven Perner Dan
Milner Stephan Wagner Len Zon Elizabeth Patton
Dana-Farber Cancer Institute
Alumni
Martin Horstmann Tim Hemesath Min Wu Han-Fei
Ding Wade Huber Gael McGill Roydon Price Jinyan
Du Emi Nishimura John DOrazio Ian Davis Tetsu
Nobuhisa Andrew Wagner
Rutao Cui Hans Widlund Vivien Igras Laura
Poling Fatih Ozsolak Jennifer Lin
thanks to NIH! thanks to Doris Duke Foundation!
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Questions

• Sunscreen for skin cancer prevention-
• strengths/weaknesses of studies
• Sunscreen and melanoma-
• How does UV induce melanoma?
• Is the public aware of data on sunscreen and
  melanoma? Does it matter?

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Pigmented Basal Cell Carcinoma