Breast cancer is the most common cancer in women and is largely determined by molecular signaling pathways in that govern cell proliferation, metabolism and cell survival. One of the major regulators of these processes is the insulin signaling cascade, and an abnormal regulation of that pathway has all been linked to triggering the initiation, progression and therapy resistance of cancers. This study investigated expression patterns of six important genes of the insulin signaling pathway (IRS1, GRB2, GSK3 beta, KRAS, GLUT4 and PTEN) in paired tumor and adjacent control tissues of breast cancer patients ( 16 patients). RNA extraction was carried out, reverse transcription was performed and quantification was done using RT-qPCR with GAPDH as an inner control.
The outcomes indicated the spectrum of expression patterns among different patients that are indicative of the non-homogeneity of breast cancer. The GRB2 and RS1 were moderately strongly upregulated in a number of cases indicating increased proliferative signaling. It was also noted that there was an upregulation of KRAS in several samples indicating that MAPK signaling was also activated in tumor tissues. There was an increase in the expression of GLUT4, other expressions reflected a more metabolic reprogramming with an increase in glucose uptake. In contrast, PTEN was overall downregulated in most cases and GSK3B expression was atypical explaining the absence of tumor-suppressive regulation.
These results indicate a signaling imbalance in the insulin signaling pathway, involving up-regulation of oncogenic drivers and down-regulation of tumor suppressing activities that collectively foster tumor aggression. This variability illustrates the need to use patient-specific molecular profiling to discover potential biomarkers and targets of therapy. This research gives an insight into the role of regulation of insulin signaling in the development of breast cancer and this information may be used in precision medicine in the future.
Keywords: Breast cancer; Insulin signaling pathway; IRS1; GRB2; KRAS; GLUT4; GSK3β; PTEN;