The Role of Patch in Basal Cell Carcinoma

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Presentation transcript:

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) 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

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

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

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