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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
