Adipose-derived stem cells (ADSCs) inhibit the expression of anti-apoptosis proteins through up-regulation of ATF4 on breast cancer cells

BACKGROUND: While current basic studies indicate adipose-derived stem cells (ADSCs) can promote cell proliferation, clinical trials have shown no significant difference in breast cancer recurrence rates for patients with or without autologous fat grafting (AFG). In this study we attempted to explore the underlying mechanism for these contradictory results. METHODS: ADSCs and umbilical mesenchymal stem cells (UMSCs) were co-cultured with breast cancer cells (MCF-7 and MDA-MB-231), and the cell viability analyzed by CCK-8 cell proliferation assay, TUNEL assay and immunofluorescence assay. In addition, real-time quantitative polymerase chain reaction (RT-qPCR) experiments and Western blot analysis were used to detect the mRNA and protein expression of activating transcription factor 4 (ATF4) and its downstream gene (MCL1 & BCL2), respectively. RESULTS: Co-cultured ADSCs could promote cell proliferation and cell apoptosis, and up-regulate ATF4 expression both in MCF-7 and MDA-MB-231. While co-cultured UMSCs could only promote cell apoptosis in MCF-7. Interestingly, we found that when co-cultured ADSCs, the expression of MCL1 and BCL2 protein was decreased, even if their mRNA expression was up-regulated both in MCF-7 and MDA-MB-231. CONCLUSIONS: Co-cultured ADSCs can up-regulate ATF4 expression, then interfere with the translation process of MCL1 and BCL2 mRNA and induce cell apoptosis. These data provide insight into the safety characteristics of AFG.