Transcript The Role of Patched in Basal Cell Carcinoma

The Role of Patch in
Basal Cell Carcinoma
Jimmy Chen
Biology 445 Cancer Biology
Spring 2009
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
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
Patch’s role in the cell
En.wikipedia.org
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)
Basal Cell Carcinoma (BCC)
Most common type of cancer and skin cancer
 75% of skin cancers are basal cell
at-risc.org/cancer.aspx
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
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
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
En.wikipedia.org
Summary
 Sonic Hedgehog is important in the embryonic
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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