The Correlation of Mutations and Expressions of Genes within the PI3K/Akt/mTOR Pathway in Breast Cancer—A Preliminary Study

Abstract

There is an urgent need to seek new molecular biomarkers helpful in diagnosing and treating breast cancer. In this elaboration, we performed a molecular analysis of mutations and expression of genes within the PI3K/Akt/mTOR pathway in patients with ductal breast cancer of various malignancy levels. We recognized significant correlations between the expression levels of the studied genes. We also performed a bioinformatics analysis of the data available on the international database TCGA and compared them with our own research. Studies on mutations and expression of genes were conducted using High-Resolution Melt PCR (HRM-PCR), Allele-Specific-quantitative PCR (ASP-qPCR), Real-Time PCR molecular methods in a group of women with ductal breast cancer. Bioinformatics analysis was carried out using web source Ualcan and bc-GenExMiner. In the studied group of women, it was observed that the prevalence of mutations in the studied PIK3CA and AKT1 genes was 29.63%. It was stated that the average expression level of the PIK3CA, PIK3R1, PTEN genes in the group of breast cancer patients is lower in comparison to the control group, while the average expression level of the AKT1 and mTOR genes in the studied group was higher in comparison to the control group. It was also indicated that in the group of patients with mutations in the area of the PIK3CA and AKT1 genes, the PIK3CA gene expression level is statistically significantly lower than in the group without mutations. According to our knowledge, we demonstrate, for the first time, that there is a very strong positive correlation between the levels of AKT1 and mTOR gene expression in the case of patients with mutations and without mutations.

Whole exome sequencing identifies novel variants of PIK3CA and validation of hotspot mutation by droplet digital PCR in breast cancer among Indian population

“…In the present study, the expression of the PIK3CA gene was upregulated in control adjacent tissue in comparison with breast carcinoma tissue. Similar results were also found in the studies performed by Kolodziej et al and Cizkova et al [ 55 , 56 ]. The lower expression was observed, possibly due to the correlation of expression with the normal group.…”

Investigation of miR-133a, miR-637 and miR-944 genes expression and their relationship with PI3K/AKT signaling in women with breast cancer

“…The PI3K/AKT/mTOR complex is a central intracellular signaling pathway that controls essential cellular activities such as: cell metabolism, cell growth, cell proliferation, apoptosis, and angiogenesis (7). This signaling pathway consists of three main components including PI3K, AKT and mTOR (32). PI3Ks are an important family of plasma membrane-bound lipid enzymes that are activated by RTKs (receptor tyrosine kinase) and by GPCRs (G protein-coupled receptors) (17).…”

Taxifolin Targets PI3K and mTOR and Inhibits Glioblastoma Multiforme

“…Multitargeting drugs have the potential advantage of eliciting synergistic effects, especially for cancer [ 43 ]. As targeted therapies have progressed, multiple PI3K/mTOR dual inhibitors have entered clinical trials and have shown good therapeutic effects [ 44 – 47 ]. We present evidence that taxifolin is a promising dual-targeting molecule that can inhibit both mTOR and PI3K.…”