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Patched and Basal Cell Carcinoma
Matt Darch
Patched
Patched Description
• Abbreviated Ptc
• Characterized as a tumor suppressor
• Sonic Hedgehog pathway
• 12 “pass” transmembrane receptor
• Binds to a ligand (Shh)
Sonic Hedgehog Pathway
Actually named after the video game character.
Sonic Hedgehog Pathway
• Many functions during development
• Acts to set up cell fates in diverse tissues
Shh Pathway
• Ptc inhibits Smo• Protein complex binds
Gli• Gli is ubiquitnated,
and truncated• Gli binds to DNA• No transcription
Shh Pathway with Hedgehog
• Hedgehog binds Ptc• Ptc doesn’t inhibit
Smo• Smo stops the
complex from ubiquitnating Gli
• Gli binds to DNA to promote transcription
Knockouts
Ptc Knockouts
Neural tube does not close.
-/- Embryonic lethal in mice
Shh pathway target genes turned on everywhere
-/-+/-
Relevance to Cancer
Radiation Sensitivity
• Ptc +/- causes increased incidence of basal cell carcinoma, a form of skin cancer
• Tested tumorigenesis in Ptc +/- mice, by exposing to UV light
• Ptc +/- mice had BCC tumors in 4 months versus 11 months in Ptc +/+ mice.
Basal Cell Carcinoma
• Type of skin cancer
• Approximately 800,000 new cases in the United States this year
• Basal cells line the bottom most layer of epidermis
• Caused by chronic overexposure to the sun, sunburns
http://www.skincancer.org/basal/index.php
Basal Cell Carcinoma
Skin Lesion
Invading tumor
Treatments
Possible Treatments
• Prevention-WEAR SUNSCREEN!
• Basal Cell Carcinoma is easy to remove
• Removed before it can dramatically effect humans
Over inhibition of Smo:Cyclopia
ligand
Treatment Continued
• Medulloblastoma localized to brain
• Frequently inoperable
• If inactive Ptc, then use cyclopamine to artificially regulate the pathway downstream of Ptc
• Currently in Clinical Trials (Genentech and Curis)
Questions?
References
http://www.cybergoat.com/cyclopia/cyclopia.htm