Knockdown of E2F5 induces cell death via the TP53‑dependent pathway in breast cancer cells carrying wild‑type TP53.

E2F transcription factor 5 (E2F5) is a member of the E2F family of transcription factors, which are involved in regulation of various cellular processes, including cellular proliferation, apoptosis, differentiation and DNA damage response. Previously, we reported that E2F5 was aberrantly overexpressed in estrogen receptor (ER)‑negative breast cancer, especially in triple‑negative breast cancer (TNBC). In the present study, it was revealed that E2F5 gene silencing caused a significant reduction in the proliferation rate of breast cancer MCF7 (ER‑positive luminal‑type) and MDA‑MB‑231 (TNBC‑type) cells. Additional experiments demonstrated that E2F5 knockdown triggered cell death of MCF7 cells but not MDA‑MB‑231 cells. As MCF7 and MDA‑MB‑231 cells carry wild‑type and mutant TP53, respectively, and BT474 (ER‑negative, HER2‑positive type) carrying mutant TP53 exhibited similar results to MDA‑MB‑231, the possible effects of E2F5 gene depletion on cell death‑related TP53‑target gene expression were examined. Real‑time RT‑qPCR analysis revealed that knockdown of E2F5 in MCF7 cells stimulated cell death‑related transcription of TP53‑target genes such as BAX, NOXA and PUMA. For MDA‑MB‑231 and BT474 cells, E2F5 gene silencing revealed marginal effects on the expression of TP53 target genes. In addition, silencing of TP53 abrogated the effect of E2F5 silencing in MCF7 cells. Collectively, the present results indicated that E2F5 participated in the carcinogenesis of breast cancer carrying wild‑type TP53 through suppression of TP53, while E2F5 had a pro‑proliferative but not anti‑apoptotic effect on breast cancer with TP53 mutation.