Besides the involvement of mTOR activity in several cancer conditions, evidence exists that increased total mTOR protein level might be linked to some cancer conditions such as colorectal carcinoma. The increase in total mTOR protein level in colon cancer was found to be associated with enhanced tumor progression and poor prognosis. Total mTOR protein level is elevated in breast cancer cells compared to their nonmalignant counterparts. High mTOR protein level in breast cancer cells could be attributed to decreased mTOR protein degradation, increased mTOR protein expression, or both. Increased protein expression may involve an increase in the gene expression.
Here, we investigated the possibility of increased MTOR gene expression as a potential underlying cause of the elevated total mTOR protein in breast cancer cells. Our results suggest that transcription of MTOR gene is increased in the estrogen receptor positive (ER+) MCF-7 breast cancer cells compared to other breast cell lines. DNA sequencing of the MTOR promoter identified sequence variations in MCF-7 cells, which could be potentially involved in upregulation of mTOR expression. Among these variations is a truncation of guanine thymine dinucleotide (GT) n repeat region in MCF-7 cells, which might be possibly implicated in the elevated transcription of MTOR gene in these cells. Moreover, our results revealed that metformin treatment, profoundly decreased mTOR mRNA levels in MCF-7 breast cancer cells.
In conclusion, unraveling the potential mechanisms involved in the regulation of mTOR expression in breast cancer cells could provide an avenue for optimizing the efficacy of breast cancer treatment regimens.
Key-words:
Breast cancer - metformin - MTOR gene expression.
