GDC-0941 downregulated the key components of the cell cycle machinery, such as cyclin D1, upregulated the apoptotic markers and inhibited cell motility on three cell lines with PIK3CA Mutation or HER2 amplification.
Neither CCND1 amplification nor cyclinD1 expression was associated with tumor size, pathological node status or HER2 amplification, but high CCND1 amplification (Copy Number Gain (CNG) > or = 8) was associated with high tumor grade (p = 0.005; chi square 7.915, 2 df) and worse prognosis by Nottingham Prognostic Index (p = 0.001; 2 sample t-test).
A minor subset of these tumors shows beta-catenin nuclear accumulation in association with increased expression of MMP-7, but not of cyclin D1, independent of EGFR and HER-2 gene amplification or expression.
HER2/neu amplification was negatively correlated with oestrogen receptor (ER) and progesterone receptor (PR) status (P less than 0.0001; for both), c-myc amplification was more prevalent in the PR-negative subpopulation (P less than 0.05) and int-2/bcl-1 amplification was positively correlated with ER status (P less than 0.001).