TFDP3 regulates the apoptosis and autophagy in breast cancer cell line MDA-MB-231

PLoS One. 2018 Sep 20;13(9):e0203833. doi: 10.1371/journal.pone.0203833. eCollection 2018.

Abstract

Cancer/testis antigen TFDP3 belongs to the transcription factor DP(TFDP) family. It can bind to E2F family molecules to form a heterodimeric transcription factor E2F/TFDP complex. The complex is an important regulatory activator of cell cycle, involved in the regulation of cell proliferation, differentiation, apoptosis and other important physiological activities. In addition, TFDP3 has also been found to be a tumor-associated antigen that only expresses in malignant tumor tissue and normal testicular tissue; Thus, it is closely related to tumor occurrence and development. In this study, our group investigated the expression of TFDP3 in mononuclear cell samples from a variety of tissue-derived malignant tumors, breast cancer and benign breast lesions. The results show that TFDP3 is expressed in the malignant form of various tissues. Moreover, our recent research had focused on the ability of TFDP3 to influence the drug resistance and apoptosis of tumor cells. To further clarify the mechanisms involved in tumor resistance, this study also examined the expression of TFDP3 and tumor cell autophagy regulation; Autophagy helps cells cope with metabolic stress (such as in cases of malnutrition, growth factor depletion, hypoxia or hypoxia) removes erroneously folded proteins or defective organelles to prevent the accumulation of abnormal proteins; and removes intracellular pathogens. Our results showed that TFDP3 expression can induce autophagy by up-regulating the expression of autophagic key protein LC3(MAP1LC3) and increasing the number of autophagosomes during chemotherapy of malignant tumors. Then, DNA and organelles damage caused by the chemotherapy medicine are repaired. Thus, TFDP3 contributes toward tumor cell resistance. When siRNA inhibits TFDP3 expression, it can reduce cell autophagy, improving the sensitivity of tumor cells to chemotherapy drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Autophagy / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • E2F1 Transcription Factor / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Microtubule-Associated Proteins / metabolism
  • Transcription Factor DP1 / metabolism*
  • Transcription Factor DP1 / physiology*
  • Transcription Factors / metabolism
  • Transcriptional Activation / genetics
  • Transcriptome / genetics

Substances

  • E2F1 Transcription Factor
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • TFDP3 protein, human
  • Transcription Factor DP1
  • Transcription Factors

Grants and funding

This work was supported by the Natural Science Foundation of Beijing Municipality, 7162099 to Yuedan Wang; Science and Technology Program of Shenzhen, JCYJ20150403110829615 to Yuedan Wang; National Natural Science Foundation of China, 81603119 to Ming Chu; Leading Academic Discipline Project of Beijing Education Bureau, BMU20110254 to Ming Chu; Fostering Talents in Basic Science of the National Natural Science Foundation of China, J1030831/J0108 to Yuedan Wang and the Natural Science Foundation of Beijing Municipality, 7174316 to Ming Chu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.