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Patched and Basal Cell Carcinoma

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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 ... – PowerPoint PPT presentation

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Title: Patched and Basal Cell Carcinoma


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 doesnt 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
Over inhibition of SmoCyclopia
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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