11396 IMGP5592

% APC

•    When the APC gene is mutated and abnormal protein is present, high levels of free cytosolic b-catenin resujt.

•    Free b-catenin migrates to the nudeus, binds to a transcription rac tor Tcf-4 or Lef-1 (T celi factor-lymphoid enhancer factor), and may activate expression of genes such as the oncogenes c-Myc and cyclin Dl.

•    The specific genes targeted are not yet known, but may indude those increasing proliferation or decreasing apoptosis.

•    As APC may be important in celi migration, abnormal APC protein may disrupt normal cellular positioning in the colonie erypt.

’ Additionally, mutations in the APC gene are thought to contribute to chromosomal instability in colorecta! cancers