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