Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells.
Application of these signatures to breast tumor gene expression data identified two novel discrete phenotypes characterized by concordant, aberrant activation of either the HER2, IGF1R, and AKT pathways ("the survival phenotype") or the EGFR, KRAS (G12V), RAF1, and BAD pathways ("the growth phenotype").
Associations between Notch-2, Akt-1 and HER2/neu expression in invasive human breast cancer: a tissue microarray immunophenotypic analysis on 98 patients.
Available paired tissue samples from breast tumors known to harbor mutations underwent massARRAY genotyping (n = 70) to identify PIK3CA and AKT1(E17K) mutations.
By using PCR target sequence enrichment and next-generation sequencing technology, we sequenced AKT1 promoter region in pairs of breast tumor and normal tissues from 95 unselected Chinese breast cancer patients.
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.
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.
For example, although signaling and metabolic profiles of breast tumors with PIK3CA or AKT1 mutations are, as expected, highly similar, they display markedly different, sometimes even opposite, profiles to those with ERBB2 or EGFR amplifications.
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.
In addition, inhibitors to the AKT/IGF-1R signaling pathways may provide alternative approaches to block escape pathways and restore hormone sensitivity in resistant breast tumors.
Increased level of phosphorylated akt measured by chemiluminescence-linked immunosorbent assay is a predictor of poor prognosis in primary breast cancer overexpressing ErbB-2.
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.
It is overexpressed in high-risk preneoplastic lesions and in primary breast tumors where it correlates with HER2 overexpression and an activated status of AKT and MAPK.