ABSTRACT
HER3 belongs to the human epidermal growth factor receptor (HER) family which also includes HER1/EGFR/erbB1, HER2/erbB2, and HER4/erbB4. As a unique member of the HER family, HER3 lacks or has little intrinsic tyrosine kinase activity. It frequently co-expresses and forms heterodimers with other receptor tyrosine kinases (RTKs) in cancer cells to activate oncogenic signaling, especially the PI-3K/Akt pathway and Src kinase. Elevated expression of HER3 has been observed in a wide variety of human cancers and associates with a worse survival in cancer patients with solid tumors. Studies on the underlying mechanism implicate HER3 expression as a major cause of treatment failure in cancer therapy. Activation of HER3 signaling has also been shown to promote cancer metastasis. These data strongly support the notion that therapeutic inactivation of HER3 and/or its downstream signaling is required to overcome treatment resistance and improve the outcomes of cancer patients.
ABSTRACT
Objective To explore the role and mechanism of long non-coding RNA (lncRNA)RP11-316M1.12 in breast cancer cells.Methods Bioinformatics analysis was performed to varify RP11-316M1.12 expression pattern in breast cancer tissues and normal tissues.Quantitative real time polymerase chain reaction (qRT-PCR) assay was used to check the expression level of RP11-316M1.12 in breast cancer cells and tissues.Further,the correlationship between RP11-316M1.12 expression and clinical paremeters of breast cancer was analysed according to RP11-316M1.12 level.RP11-316M1.12 was overexpressed in MCF-7 cells,and RP11-316M1.12 was knocked down in MDA-MB-231 cells.Transwell method was used to detect the invasive ability of these cells.Western blot was used to detect the expression of epithelialmesenchymal transition (EMT) markers in these cells.Results Gene Expression Profiling Interactive Analysis (GEPIA) database suggested that RP11-316M1.12 was highly expressed in breast cancer tissues than that in normal tissues.The similar results were got in 65 cases of breast cancer tissues and 23 cases of normal tissues by qRT-PCR assay.Meanwhile,we found that RP11-316M1.12 was enhanced in breast cancer cells than that in normal epithelial cell and RP11-316M1.12 expression is related to TNM stage and distant metastasis in breast cancer.Transwell assay demonstrated that RP11-316M1.12 significantly enhanced breast cancer cells invasion.Mechanismly,over expression of RP11-316M1.12 can remakably downregulated E-cadherin,enhanced ZEB1 and Vimentin expression in these cells.Conclusions RP11-316M1.12 was enhanced in breast cancer,and RP1 1-316M1.12 could accelerate invasion of breast cancer cells.
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Objective To investigate the role of epidermal growth factor receptor 3 (ErbB3) and insulin-like growth factor-1 receptor (IGF1R) in enhancing the resistance of Herceptin in human breast cancer.Methods HRG (Heregulin,the ligand of ErbB3) or IGF2 (insulin-like growth factor2,the ligand of IGF1R) was correspondingly added into breast cancer cells SKBR3 and BT474,and then 3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and were performed in these cells to evaluate the sensitivity of these cells to Herceptin.Furthermore,we used HRG or IGF2 antibodies to inhibit their joint receptors in Herceptin-resistant breast cancer cells SKBR3/POOL2 and BT474/HR20.Finally,the sensitivity of these treated cells to Herceptin was detected via MTS assay.HRG or IGF2 was added into breast cancer cell BT474,and co-IP assay was used to detect the expressions of ErbB3 and IGF1R which combined with ErbB2.Results The treatment groups used HRG or IGF2 enhanced the resistance of Herceptin in Herceptin-sensitive breast cancer cells.On the other hand,we used antibodies of HRG and IGF2 to block their combining with their receptors in Herceptin-resistant breast cancer cells,the cells became more sensitive to Herceptin.BT474 cell was treated with HRG or IGF2.The expressions of ErbB3 and IGF1R which combined with ErbB2 were increased.Conclusions The formation of heterodimers ErbB2/ErbB3 and ErbB2/IGF1R might enhance the resistance of Herceptin in ErbB2-overexpression human breast cancers.
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Insecticidal protein genes from Bacillus thuringiensis are currently the most widely used insect-resistant genes. They have been transferred to many crops for breeding and production. Among them, cotton, maize, potato and other insect-resistant crops are commercialized, creating considerable economic benefit. In this review, we summarized advances in identifying functional genes and transgenic crops for insect resistance, compared different strategies for enhancing vigor of insecticidal protein and utilizing gene stacking as well as listing valuable groups of stacked genes. In addition, the methods for multiple gene transformation was discussed.