The activation of the oncogene PIK3CA and the loss of regulators of AKT including the tumor suppressor gene PTEN are mutations commonly found in breast tumors.
Resveratrol-induced cell inhibition of growth and apoptosis in MCF7 human breast cancer cells are associated with modulation of phosphorylated Akt and caspase-9.
Inhibiting AKT or preventing SIRT6 phosphorylation by mutating Ser(338) prevented the degradation of SIRT6 mediated by MDM2, suppressed the proliferation of breast cancer cells in culture, and inhibited the growth of breast tumor xenografts in mice.
Estrogens induce breast tumor cell proliferation by directly regulating gene expression via the estrogen receptor (ER) transcriptional activity and by affecting growth factor signaling pathways such as mitogen-activated protein kinase (MAPK) and AKT/mammalian target of rapamycin Complex1 (mTORC1) cascades.
Increased level of phosphorylated akt measured by chemiluminescence-linked immunosorbent assay is a predictor of poor prognosis in primary breast cancer overexpressing ErbB-2.
Together, this study demonstrates two previously uncharacterized factors AK023948 and DHX9 as important players in the AKT pathway, and that their upregulation may contribute to breast tumour progression.
However, here we show through phosphoprotein profiling and functional genomic studies that many PIK3CA mutant cancer cell lines and human breast tumors exhibit only minimal AKT activation and a diminished reliance on AKT for anchorage-independent growth.
These findings suggest N-cadherin/FGFR has a pivotal role in promoting metastasis through differential regulation of ERK and AKT, and underscore the potential for targeting the FGFR in advanced ErbB2-amplified breast tumors.
Similar results were also seen between liver metastases and primary breast tumors [AKT (S473) <i>P</i> < 0.01, mTOR (S2448) <i>P</i> < 0.01, 4EBP1 (S65) <i>P</i> = 0.01].
These data suggest that activation of the ERBB2-PI3K-AKT pathway by loss of PTEN at early stages of tumorigenesis promotes the formation of breast tumors with apocrine features.
Associations between Notch-2, Akt-1 and HER2/neu expression in invasive human breast cancer: a tissue microarray immunophenotypic analysis on 98 patients.
This bifurcation of signaling complexes from distinct ShcA pools transduces non-redundant signals that integrate the AKT/mTOR and SFK pathways to cooperatively increase breast tumor growth and resistance to tyrosine kinase inhibitors, including lapatinib and PP2.
Expression of EXO1 module was found as indicative of elevated cell proliferation, genomic instability, activated RAS/AKT/MYC/E2F1 signaling pathways and loss of p53 activity in breast tumors. mRNA-drug connectivity analysis indicates inhibition of RAS/PI3K as a possible targeted therapeutic approach for the patients with activated EXO1 module in breast tumors.