Mitochondrial transcription factor A contributes to cisplatin resistance in patients with estrogen receptor-positive breast cancer

Abstract

Previous studies have reported that triple-negative breast cancer is more sensitive to cytotoxic treatment, compared with estrogen receptor (ER)‑positive cancer. However, the underlying molecular mechanisms remain to be fully elucidated. In the present study, we employed reverse transcription‑quantitative polymerase chain reaction, western blot and in vivo assays to investigate the underlying mechanisms. The sensitivities of cells to cisplatin were examined in ER-positive and ER‑negative breast cancer cells, and it was found that the ER‑negative cells were more sensitive to cisplatin, compared with the ER‑positive cells. In addition, it was found that mitochondrial transcription factor A (TFAM), which functions in mitochondrial DNA replication and repair, was expressed at a high level in ER‑positive cell lines and patient tissues, compared with ER‑negative cell lines and tissues. It was also found that the sensitivity to cisplatin was decreased when TFAM was knocked down in the breast cancer cells, and these effects were reversed when TFAM was reintroduced to the cells. Similar results were observed in xenograft tumors. The results of the present study provided evidence that resistance to cisplatin chemotherapy in ER‑positive breast cancer may be through TFAM and indicated that TFAM may be a target for chemoresistance in patients with breast cancer. These findings offer potential guidance for chemotherapy in patients with breast cancer.

Down-Regulation of MicroRNA-214 Contributed to the Enhanced Mitochondrial Transcription Factor A and Inhibited Proliferation of Colorectal Cancer Cells

“…TFAM is reported to be associated with tumorigenesis in breast, cervical, prostate, small cell lung cancers [12][13][14][15][16]. Also, frequent frameshift mutations in the coding mononucleotide repeat of TFAM was demonstrated in sporadic CRC derived cell lines and CRC tissues [17,18].…”

Mitochondria Transcription Factor A: A Putative Target for the Effect of Melatonin on U87MG Malignant Glioma Cell Line

“…Glioblastoma is a very aggressive type of cancer with a very low survival rate. Therefore, new therapeutic targets have been investigated, and TFAM is a strong candidate target since its expression is altered in several types of cancer, including glioma [ 13 , 15 ], colorectal cancer [ 63 ], epithelial ovarian carcinoma [ 66 ], bladder cancer [ 67 ], breast cancer [ 68 ], lung cancer [ 41 , 69 ], and colon cancer [ 70 ]. Moreover, the use of melatonin in the treatment of cancer has shown promising results.…”

Mitochondrial HMG-Box Containing Proteins: From Biochemical Properties to the Roles in Human Diseases

“…Overexpression of TFAM increases the mtDNA copy number [ 132 ] and also causes significant modifications in mtDNA transcription and replication in mt-nucleoids reconstituted in vitro [ 299 ] and in cultured human cells [ 133 ]. Neurodegenerative model studies showed that the overall mtDNA levels were reduced by ~30% with an even more significant reduction (~50%) of TFAM protein levels.…”