IRF1 Negatively Regulates Oncogenic KPNA2 Expression Under Growth Stimulation and Hypoxia in Lung Cancer Cells.

PURPOSE: Karyopherin alpha 2 (KPNA2) has been reported as an oncogenic protein in numerous human cancers and is currently considered a potential therapeutic target. However, the transcriptional regulation and physiological conditions underlying KPNA2 expression remain unclear. The aim of the present study was to investigate the role and regulation of interferon regulatory factor-1 (IRF1) in modulating KPNA2 expression in lung adenocarcinoma (ADC). MATERIALS AND METHODS: Bioinformatics tools and chromatin immunoprecipitation were used to analyze the transcription factor (TF) binding sites in the KPNA2 promoter region. We searched for a potential role of IRF1 in non-small-cell lung cancer (NSCLC) using Oncomine and Kaplan-Meier Plotter datasets. qRT-PCR was applied to examine the role of IRF1 and signaling involved in regulating KPNA2 transcription. Western blotting was used to determine the effects of extracellular stimulation and intracellular signaling on the modulation of KPNA2-related TF expression. RESULTS: IRF1 was identified as a novel TF that suppresses KPNA2 gene expression. We observed that IRF1 expression was lower in cancerous tissues than in normal lung tissues and that its low expression was correlated with poor prognosis in NSCLC. Notably, both ataxia telangiectasia mutated (ATM) and mechanistic target of rapamycin (mTOR) inhibitors reduced KPNA2 expression, which was accompanied by increased expression of IRF1 but decreased expression of E2F1, a TF that promotes KPNA2 expression in lung ADC cells. IRF1 knockdown restored the reduced levels of KPNA2 in ATM inhibitor-treated cells. We further demonstrated that epidermal growth factor (EGF)-activated mTOR and hypoxia-induced ATM suppressed IRF1 expression but promoted E2F1 expression, which in turn upregulated KPNA2 expression in lung ADC cells. CONCLUSION: IRF1 acts as a potential tumor suppressor in NSCLC. EGF and hypoxia promote KPNA2 expression by simultaneously suppressing IRF1 expression and enhancing E2F1 expression in lung ADC cells. Our study provides new insights into targeted therapy for lung cancer.

[Contrast-enhanced ultrasound findings of breast cancer].

OBJECTIVE: To study the manifestation of breast cancers of different sizes in contrast-enhanced sonography. METHODS: Eighty-four patients with breast cancers were examined by contrast-enhanced ultrasound. Among them, the tumor diameter was beyond 2.0 cm in 50 cases, and no greater than 2.0 cm in the rest cases. The time-intensity curve (TIC) on the enhanced images was analyzed quantitatively, and the relations between the type of TIC and the enhancement patterns of the tumors were analyzed. RESULTS: The enhancement patterns of the breast cancers showed significant difference between patients with tumor diameter beyond 2.0 cm and those with smaller tumors (P<0.01), but the other parameters were comparable between the two groups (P>0.05). CONCLUSION: The enhancement patterns of breast cancers differ between tumors with sizes over 2.0 cm and smaller tumors, and differential analysis is suggested in the diagnosis of breast cancer using contrast-enhanced ultrasound.