Abstract
Introduction: Trastuzumab resistance is a major obstacle encountered in human epidermal growth factor receptor 2 (HER2)-positive breast cancer therapy. Long non-coding RNAs (lncRNAs) have been confirmed to play important roles in both tumorigenesis and tumor development. However, whether lncRNAs are associated with trastuzumab resistance is not yet clear. Subjects and Methods: We evaluated trastuzumab sensitivity in breast cancer cell lines, SKBR3, HCC1954, and MDA-MB-231. We also evaluated H19 expression in these cell lines after treatment with different trastuzumab concentrations. Besides, H19 was downregulated to investigate its role in cell viability and trastuzumab sensitivity and a trastuzumab resistance cell line was cultured to verify the effect of H19 in trastuzumab resistance. Forty-eight HER2-positive breast cancer patients treated with trastuzumab in the first-line setting were selected retrospectively to explore the relationship between H19 expression and tumor-node-metastasis (TNM) stage as well as trastuzumab resistance. Results: H19 is a trastuzumab-responsive lncRNA and its expression was upregulated in a trastuzumab-resistant breast cancer cell. Downregulation of H19 restored the sensitivity of trastuzumab-resistant cells to this drug. The expression of H19 significantly correlated with TNM stage. Patients with higher expression of H19 showed an evidently shorter progression-free survival than those with low H19 expression. H19 overexpression was negatively correlated to the trastuzumab-therapy response. Conclusions: Our results provide evidence for the H19-mediated regulation of trastuzumab resistance in HER2-positive breast cancer cells. H19 could act as a potential predictive biomarker for HER2-positive breast cancer patients, and downregulation of H19 could reverse trastuzumab resistance and enhance the inhibitory function of this drug.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan