LMO4 inhibits p53-mediated proliferative inhibition of breast cancer cells through interacting p53

Aims: The LIM domain only proteins (LMOs) which consist of four members (LMO1-LMO4) are a family of nuclear transcription coregulators that are characterized by the exclusive presence of two tandem LIM domains and no other functional domains. They regulate gene transcription by functioning as linker or scaffolding proteins by virtue of their LIM domains and are involved in the formation of multiprotein complexes with several DNA-binding factors and transcriptional regulatory proteins. In the present study, we tried to find the physical interaction between p53 and LMO4, and the effect of LMO4 on p53-mediated proliferative inhibition of breast cancer cells. Main methods: FCM analysis was developed to detect the apoptosis of breast cancer cells after adriamycin (ADR) treatment. RT-PCR and Western blot analysis were performed to detect the expression of LMO4 and p53-related genes and proteins. Immunoprecipitation assay was used to detect the interaction between LMO4 and p53. Colony formation assay was developed to detect the proliferation of breast cancer cells. Key findings: We found that p53 was induced, but LMO4 was down-regulated in response to ADR. We also found that enforced expression of p53 inhibited the expression of LMO4, suggesting that LMO4 is a direct transcriptional target of p53. Furthermore, LMO4 can interact with p53 and inhibit p53-mediated inhibition of colony formation of breast cancer MDA-MB-453 cells. Significance: The present study showed that LMO4 is a direct target of p53 and inhibits p53-mediated proliferative inhibition of breast cancer cells through interacting p53. (C) 2012 Elsevier Inc. All rights reserved.