“Activation of the MAP-kinase and AKT signaling pathways in Breast Carcinoma in vivo”.

PhD Thesis: “Activation of the MAPkinase and AKT signaling pathways in Breast carcinoma in vivo”. The Ras/Raf/MEK/ERK and PI3K/PTEN/AKT signaling cascades play critical roles in the transmission of signals from growth factor receptors to regulate gene expression and prevent apoptosis. Components of these pathways are mutated or aberrantly expressed in most human cancers (e.g., Ras, B-Raf, PI3K, PTEN, Akt). Also, mutations occur in genes encoding upstream receptors (e.g., EGFR and Flt-3) and novel fusion genes, resulting from chimeric chromosomal translocations (e.g., BCR-ABL), may transmit their signals through these cascades. These pathways interact with each other to regulate tumor growth. For example, PTEN inactivation may contribute to suppression of the Raf/MEK/ERK cascade due to the ability of elevated activated Akt levels to phosphorylate and inactivate Raf-1. The understanding of the signaling pathways (MAPK and PI3K/AKT pathway) involved in breast cancer tumorigenesis may help to find new predictive factors to develop new treatments. Recent evidence suggest that the PI3K/AKT pathway may play a major role in breast cancer cancerogensis and at the same time could represent an ideal target for novel drugs