The PATCHED (Ptc) The PATCHED (Ptc) GeneGene

Brendan McQuellonBrendan McQuellon

What is PATCHWhat is PATCH

• Transmembrane surface receptor

• Binds ligands of Hedgehog(Hh) familyWeinberg, 2007

Normal Ptc RoleNormal Ptc Role

• Controls cell fate by inhibiting Hh/Shh signaling

• Inhibits the transcription of Hh/Shh target genes

• Can regulate the cell cycle

Shh/Ptc/Gli pathwayShh/Ptc/Gli pathway

Weinberg, 2007

http://www.armchairempire.com/images/feature-articles/Weekly-Top-10/pub-crawl/sonic-hedgehog.jpg

Shh/Ptc/Gli pathwayShh/Ptc/Gli pathway

Weinberg, 2007

http://www.armchairempire.com/images/feature-articles/Weekly-Top-10/pub-crawl/sonic-hedgehog.jpg

Sonic hedgehog and Patched Sonic hedgehog and Patched regulate neural developmentregulate neural development

http://scienceblogs.com/pharyngula/2007/03/basics_neurulation.phpwww.pressthebuttons.com/

Sonic hedgehog and Patched Sonic hedgehog and Patched regulate neural developmentregulate neural development

http://scienceblogs.com/pharyngula/2007/03/basics_neurulation.phpwww.pressthebuttons.com/

Sonic hedgehog and Patched Sonic hedgehog and Patched regulate neural developmentregulate neural development

http://scienceblogs.com/pharyngula/2007/03/basics_neurulation.php

www.pressthebuttons.com/

Sonic hedgehog and Patched Sonic hedgehog and Patched regulate neural developmentregulate neural development

Goodrich et al, 2007 www.pressthebuttons.com/

How KO’s were madeHow KO’s were made

Goodrich et al., 1997

Heterozygous MiceHeterozygous Mice

Goodrich et at., 1997

Heterozygous MiceHeterozygous Mice

Goodrich et at., 1997

How does Ptc relate to cancer?How does Ptc relate to cancer?

• Gorlin Syndrome– Basal Cell Carcinomas

– Medulloblastomas

• Sporadic Instances

• Ionizing Radiation

http://www.medicalecology.org/images/atmosphere/skincancer1.gif

How does Ptc relate to cancer?How does Ptc relate to cancer?

• Meningiomas, Breast and Esophageal carcinomas

• Shh/Ptc pathway hyperactive in many other cancers