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Basal Cell Carcinoma and Patched
•Basal Cell Carcinoma is the most common skin
cancer, and possibly the most common cancer of
all
http://www.skincancer.org/basal/index.php
Normal Skin Cells
Basal Cell Carcinoma
• Like most skin cancers, BCC is primarily
caused by sun exposure, specifically UVB rays
• These rays cause mutations in DNA including
deletions and substitutions
• The Patched gene is a tumor suppressor, like
Retinoblastoma
• Therefore, both copies of Patched must be
mutated in order to cause a tumor
• Nevoid Basal Cell Carcinoma is the inherited
form of the patched mutation, and results in
tumor formation in many tissues
http://www.dermoncology.com/tumors/tu
mor%20albums/b6.htm
The Sonic Hedgehog-Patched
Pathway
Shh
Ptch
Smo
Cytoplasm
Microtubules
Gli1
Nucleus
• The Sonic Hedgehog pathway is involved in
many processes, most importantly in midline
patterning and dorsal-ventral nervous system
development
www.jhu.edu/~jhumag/0297web/
scitech.html
Veratrum californicum (California
False Hellebore)
•Contains an alkaloid
called cyclopamine
•Cyclopamine binds
directly to Smo and
inhibits the Shh pathway
www.csdl.tamu.edu/FLORA/ imaxxmln.htm
Cyclopia in sheep
muvetmed.agr.iwate-u.ac.jp/.../ tenji/tenji9.html
When Ptch is mutated, it turns the pathway on
without binding Shh- more patched is transcribed
Ptch
Smo
Cytoplasm
Microtubules
Gli1
Nucleus
Possible Treatments
• Cyclopamine, and is currently in clinical trials
• Patched itself can also inhibit this pathway,
and has been effective in mice with BCC