Tripartite motif-containing 24 (TRIM24), a member of the transcription intermediary factor 1 family, is defined as a co-regulator with several nuclear receptors, such as RARα. TRIM24 has been reported to be involved in many cancers. In this study, we aimed to investigate the expression pattern and prognostic significance of TRIM24 and its relationship with RARα in esophageal squamous cell cancer (ESCC). Both mRNA and protein expression levels of TRIM24 were found to be significantly decreased in ESCC, as judged by qRT-PCR and western blot. Immunohistochemistry staining shows that the reduced TRIM24 protein is associated with lymph node metastasis (P=0.024), advance pathological TNM (pTNM) stage (P=0.046) and recurrence/metastasis (P=0.001). Upregulated TRIM24 protein predicts longer overall survival and disease-free survival (both P<0.001) and is an independent predictor for good prognosis (HR, 0.519; 95%CI, 0.341-0.788; P=0.002). TRIM24 expression has been proven remarkably to improve prediction of survival of pTNM stage in ESCC patients, especially in stage I and II. However, no significant relationship was found between TRIM24 and RARα expression levels. In conclusion, reduced TRIM24 protein is associated with poor survival in ESCC patients, suggesting TRIM24 protein is a potential prognostic biomarker for ESCC.

Epirubicin (EPI) is widely used for triple negative breast cancer (TNBC), but a substantial number of patients develop EPI resistance that is associated with poor outcome. The underlying mechanism for EPI resistance remains poorly understood. We have developed and characterized an EPI-resistant (EPI-R) cell line from parental MDA-MB-231 cells. These EPI-R cells reached stable growth in the medium containing 8 μg/ml of EPI. They overexpressed P-glycoprotein (P-gp) and contained numerous autophagic vacuoles. The suppression of P-gp overexpression and/or autophagy restored the sensitivity of these EPI-R cells to EPI. We further show that autophagy conferred resistance to EPI on MDA cells by blocking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated pro-apoptotic signals. Together, these results reveal a synergistic role of P-gp, autophagy, and NF-κB pathways in the development of EPI resistance in TNBC cells. They also suggest that blocking the P-gp overexpression and autophagy may be an effective means of reducing EPI resistance.

BackgroundEsophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related death, and new prognostic biomarkers are urgently needed. Apoptosis-stimulating P53-binding protein 1 (ASPP1) and 2 (ASPP2) have been reported to play important roles in the development, progression, metastasis, and prognosis of cancers, but their roles in ESCC have not been elucidated. In this study, we examined the expression of ASPP1 and ASPP2 in ESCC to evaluate their prognostic values.MethodsThe protein expression of ASPP1, ASPP2, and P53 in 175 specimens of ESCC was detected using immunohistochemical staining; their expression in cancerous and noncancerous tissues was scored according to the staining intensity and the percentage of stained cells. The associations of ASPP1, ASPP2, and P53 with clinicopathologic parameters, overall survival (OS), and disease-free survival (DFS) were analyzed.ResultsThe protein expression levels of ASPP2 and P53 were significantly higher in cancerous tissues than in paired noncancerous tissues (P < 0.001), whereas the expression levels of ASPP1 in the two groups were similar. In ESCCs, ASPP1 expression was significantly associated with histological differentiation (P = 0.002) and invasive depth (P = 0.014); ASPP2 expression was associated with age (P = 0.029) and histological differentiation (P < 0.001); and P53 expression was associated with age (P = 0.021) and tumor size (P = 0.040). No correlations were found between ASPP1, ASPP2, and P53 expression. Survival analysis revealed that high ASPP2 expression was significantly associated with increased 5-year OS (P = 0.001) and DFS rates (P = 0.010) and that high P53 expression was significantly associated with a reduced 5-year DFS rate of ESCC patients (P = 0.015). Multivariate Cox analysis indicated that ASPP2 was an independent predictor of OS [hazard ratio (HR): 0.541, 95% confidence interval (CI) 0.363–0.804] and DFS (HR: 0.599, 95% CI 0.404–0.888) of ESCC patients and that P53 was an independent predictor of DFS (HR: 2.161, 95% CI 1.100–4.245).ConclusionsASPP1 might be involved in the progression of ESCC, and ASPP2 was a potential prognostic biomarker of ESCC and should be evaluated in future studies.