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Tamoxifen (TAM) resistance to invasive lobular cell carcinoma is a challenge for breast cancer treatment. This study explored the role of Aldo-keto reductase family 1 (AKR1) family in tamoxifen-resistant aggressive lobular breast cancer based on data mining. | Xu et al. BMC Cancer 2021 21 1321 https doi.org 10.1186 s12885-021-09040-8 RESEARCH Open Access The role of AKR1 family in tamoxifen resistant invasive lobular breast cancer based on data mining Dong Xu Yiqi Zhang and Feng Jin Abstract Background Tamoxifen TAM resistance to invasive lobular cell carcinoma is a challenge for breast cancer treat- ment. This study explored the role of Aldo-keto reductase family 1 AKR1 family in tamoxifen-resistant aggressive lobular breast cancer based on data mining. Methods TAM-resistant invasive lobular breast cancer gene chip was downloaded from the Gene Expression Omnibus GEO database accession-numbered as GSE96670 . The online analytical tool GEO2R was used to screen for differentially expressed genes in TAM-resistant invasive lobular breast cancer cells and TAM-sensitive counterparts. A protein-protein interaction PPI networks were constructed using the STRING online platform and the Cytoscape software. GeneMANIA and GSCALite online tools were used to reveal the potential role of these hub genes in breast cancer progression and TAM resistance development. And the used the GSE67916 microarray data set to verify the differentially expression of these hub genes in breast cancer. The protein expression levels of AKR1C1 AKR1C2 and AKR1C3 in TAM-sensitive and resistant breast cancer cells were compared. The TAM sensitivity of breast cancer cells with or without AKR1C1 AKR1C2 or AKR1C3 gene manipulation was evaluated by cell viability assay. Results A total of 184 differentially expressed genes were screened. Compared with TAM sensitive breast cancer cells 162 were up-regulated and 22 were down-regulated. The study identified several hub genes in the PPI network that may be involved in the development of TAM resistance of breast cancer including signal transducer and activator of transcription 1 STAT1 estrogen receptor alpha ESR1 fibronectin1 FN1 cytochrome P4501B1 CYP1B1 AKR1C1 AKR1C2 AKR1C3 and uridine diphosphate .