Promyelocytic leukemia zinc finger triggers ATP-binding cassette subfamily E member 1-mediated growth inhibition in breast cancer cells

摘要

The promyelocytic leukemia zinc finger (PLZF) protein is a transcription factor that is involved in a number of biological processes, including those regulating cellular growth; however, little is known regarding how it achieves its inhibitory effect in different cell and tissue types. It has previously been demonstrated that PLZF expression levels become diminished during the oncogenic transformation of certain tissue types and thus, may serve as a hallmark for tumor aggressiveness. To examine this in breast cancer, survival curves from available oncology databases were analyzed and demonstrated that PLZF expression was positively associated with increased survival in patients with breast cancer. The mRNA and protein levels of PLZF were also revealed to be associated with the tumorigenicity of four breast cancer cell lines. Since ATP-binding cassette subfamily E member 1 (ABCE1), also known as RNase L inhibitor, has been determined to be a target gene of PLZF, the present study also investigated whether the tumor suppressive effect of PLZF was associated with ABCE1 expression. PLZF was revealed to downregulate the expression of ABCE1 in vitro, which relieved the inhibitory effect of ABCE1 on the ribonuclease L enzyme. Finally, it was concluded that PLZF expression caused an ABCE1-mediated increase in cellular cytotoxicity, as demonstrated by a reduction in the proliferation rate of breast cancer cell lines. The results of the present study are important for understanding how PLZF exerts its final inhibitory actions in breast cancer cells, and potentially in other solid tumors, through the modulation of immunological pathways.