1. The Role of Patch in Basal Cell Carcinoma
Jimmy Chen
Biology 445 Cancer Biology
Spring 2009

2. Sonic Hedgehog (SHH) Signaling Pathway
Very important during embryonic development
Nervous system
Skeletal system
Muscular system
Promoting proliferation of adult stem cells
Development of limbs

3. Patch’s roles in the cell
A Transmembrane protein of the hedgehog pathway
Tumor Suppressor
A key suppressor in the hedgehog pathway
Inhibits the activation of the protein Smoothened (Smo)
This inhibition is relieved with the binding of the ligand Sonic Hedgehog to Patch
Patch indirectly affects the transcription factor GLI

4. Patch’s role in the cell
En.wikipedia.org

5. Homologous Recombination in Mice
Patch -/- mutation is lethal
Essential for survival
Severe defects in the nervous and cardiovascular system
Patch +/- mutation
Developmental anomalies
Embryonic body overgrowth
Skeletal irregularities
Goodrich et al, Science 227, 1109 (1997)

6. Basal Cell Carcinoma (BCC)
at-risc.org/cancer.aspx
Most common type of cancer and skin cancer
75% of skin cancers are basal cell carcinomas
BCC do not metastasize to other organs through the blood stream but it can still spread to nearby organs.
More commonly seen on areas of the skin regularly exposed to sunlight.
90% chance of successfully treating BCC

7. Patch’s regulation of the cell cycle
Patch mediates Cyclin B location
Inhibiting cell proliferation
Lack of regulation from Patch results in No restriction Mitosis
Proliferation occurs
En.wikipedia.org

8. Patch’s role in Cancer
Patch+/- mutation Caused developmental abnormalities Increased chance of developing basal cell carcinoma Also increased chances of developing medulloblastoma Ionizing Radiation Haploinsufficiency Loss of Heterozygosity

9. Changes in over expression of SHH or GLI or the inhibition of the ability for SMO to be regulated can cause cancer also
En.wikipedia.org

10. Summary
Sonic Hedgehog is important in the embryonic developmental pathway
Patch is a key suppressor in the SHH pathway and essential for embryonic growth
Patch directly regulates cell cycle progression
Basal cell carcinoma is the most common type of cancer
Patch can still be present and cause BCC
Other mutations in the SHH pathway along with decreased expression of Patch can cause BCC