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Patched and Basal Cell Carcinoma

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.

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Patched and Basal Cell Carcinoma

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  1. Patched and Basal Cell Carcinoma Matt Darch

  2. Patched

  3. Patched Description • Abbreviated Ptc • Characterized as a tumor suppressor • Sonic Hedgehog pathway • 12 “pass” transmembrane receptor • Binds to a ligand (Shh)

  4. Sonic Hedgehog Pathway Actually named after the video game character.

  5. Sonic Hedgehog Pathway • Many functions during development • Acts to set up cell fates in diverse tissues

  6. Shh Pathway • Ptc inhibits Smo • Protein complex binds Gli • Gli is ubiquitnated, and truncated • Gli binds to DNA • No transcription

  7. 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

  8. Knockouts

  9. Ptc Knockouts -/- +/- Neural tube does not close. -/- Embryonic lethal in mice Shh pathway target genes turned on everywhere

  10. Relevance to Cancer

  11. 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.

  12. 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

  13. Basal Cell Carcinoma Skin Lesion Invading tumor

  14. Treatments

  15. Possible Treatments • Prevention-WEAR SUNSCREEN! • Basal Cell Carcinoma is easy to remove • Removed before it can dramatically effect humans

  16. ligand Over inhibition of Smo:Cyclopia

  17. 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)

  18. Questions?

  19. References http://www.cybergoat.com/cyclopia/cyclopia.htm

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