PO-231 mTOR activity differences and related metabolic activity in human breast cancer cell lines

Introduction The mTOR (mammalian target of rapamycin) is a receptor tyrosine kinase which plays an important role in cell growth regulation, proliferation and tumour cell survival in cancer cells. Differences of mTOR activity were described in tumours. mTOR dependent and independent metabolic activity of tumour cells could be essential in survival and therapy resistance of breast cancer. Changes of mTOR and metabolic activity of breast cancer could correlate to the patients’ treatment outcome. Material and methods In our work, the correlations between the metabolic phenotype and mTOR activity of breast cancer cell lines were studied. Furthermore, the expressions of mTOR activity related proteins and several metabolic transporter, enzymes were studied by Western blot, ICC and IHC using breast cancer cell lines and human tissue samples. The metabolic phenotypes were also analysed using LC-MS. Moreover, the effect of mTOR, metabolic inhibitors and chemotherapeutics were also studied in vitro. Results and discussions Subtypes independent differences in mTORC1/C2 complex and metabolic activities were detected in breast cancer cell lines. Certain cell lines were characterised with high glucose uptake, high mTORC1 complex activity and high lactate production, while other cell lines showed balanced mTORC1 and mTORC2 activity, well-functioning oxidative phosphorylation capacity and higher levels of TCA metabolites which were related to intact mitochondrial functions. The metabolic phenotype and mTORC1/C2 activity correlated to the detected mTOR inhibitors, metabolic inhibitors and chemotherapeutic sensitivity of breast cancer cell lines in vitro. The metabolic and mTOR activity differences can be observed in human tissue samples independently of breast carcinoma cell subtypes, as well. Conclusion Differences of metabolic and mTOR related protein levels may explain the different therapeutic sensitivity. We suggest evaluating the metabolic phenotype and mTOR activity in breast cancer subtypes, which may help to introduce therapeutic drug combinations and predict therapy resistance. Supported by STIA-KF-17(SA), Bolyai-590/2015(SA), UNKP-17-3(HZ)−17-3(KI)−17-2(DT) and EFOP-3.6.3-VEKOP-16-2017-00009.