title: 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.
authors: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors: Wei
authors: W
authors: Gao
authors: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors: Mei-Hong
authors: MH
authors: Wu
authors: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors: Ning
authors: N
authors: Wang
authors: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors: Ming-Zheng
authors: MZ
authors: Ying
authors: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors: Ying-Yi
authors: YY
authors: Zhang
authors: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors: Jing
authors: J
authors: Hua
authors: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors: Liu
authors: L
authors: Chuan
authors: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors: Ya-Jie
authors: YJ
authors: Wang
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D051266:Nuclear Respiratory Factor 1 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D051266:Nuclear Respiratory Factor 1; D011960:Receptors, Estrogen; C499631:TFAM protein, human; D014157:Transcription Factors; D002945:Cisplatin