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- W4280493673 abstract "Abstract Tamoxifen is a first-line adjuvant endocrine drug used in the treatment of patients with estrogen receptor (ER)-positive breast cancer. The drug’s therapeutic benefit is limited by the development of resistance due to alterations in autophagy function. In this study, the role of the cAMP-dependent protein kinase inhibitor-β (PKIB) in autophagy and the development of tamoxifen-resistant breast cancer were evaluated. Expression of PKIB was assessed by RTq-PCR, Western blot analysis, and immunohistochemistry (IHC) in tamoxifen-resistant and sensitive breast cancer cell lines and clinical samples. Knockdown and overexpression of PKIB were used to determine the sensitivity to tamoxifen in vitro and the status of autophagy. Further, immunofluorescence and Western blot analysis were used to explore the tamoxifen resistance mechanism of PKIB. CREB/ATG7 signaling activation was evaluated after knocking down of PKIB in MCF7 and T47D cells. The level of PKIB expression was upregulated in the tamoxifen-sensitive breast cancer cell lines (MCF7 and T47D) and in primary tumor tissues. Knock down of PKIB decreased the sensitivity to tamoxifen both in vitro and in vivo, and significantly enhanced the autophagy level in the tamoxifen-sensitive cell lines. In contrast, overexpression of PKIB inhibited autophagy and restore tamoxifen sensitivity in tamoxifen-resistant cells. Moreover, an increase in p-CREB and ATG7 protein expression levels were observed in MCF7/si2-PKIB and T47D/si2-PKIB cells by Western blot. Finally, Kaplan-Meier curve analysis also indicated that the high level of PKIB predicts a good prognosis in breast cancer. Overall, our findings demonstrated that PKIB suppresses CREB/ATG7 activation and subsequent autophagy which could contributes to tamoxifen resistance in breast cancer." @default.
- W4280493673 created "2022-05-22" @default.
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- W4280493673 date "2022-05-11" @default.
- W4280493673 modified "2023-09-27" @default.
- W4280493673 title "PKIB regulates tamoxifen resistance in estrogen receptor-positive breast cancer through inhibition of autophagy" @default.
- W4280493673 doi "https://doi.org/10.21203/rs.3.rs-1611081/v1" @default.
- W4280493673 hasPublicationYear "2022" @default.
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