RESUMO
Endocrine treatment, particularly tamoxifen, has shown significant improvement in the prognosis of patients with estrogen receptor-positive (ER-positive) breast cancer. However, the clinical utility of this treatment is often hindered by the development of endocrine resistance. Therefore, a comprehensive understanding of the underlying mechanisms driving ER-positive breast cancer carcinogenesis and endocrine resistance is crucial to overcome this clinical challenge. In this study, we investigated the expression of MICAL-L2 in ER-positive breast cancer and its impact on patient prognosis. We observed a significant upregulation of MICAL-L2 expression in ER-positive breast cancer, which correlated with a poorer prognosis in these patients. Furthermore, we found that estrogen-ERß signaling promoted the expression of MICAL-L2. Functionally, our study demonstrated that MICAL-L2 not only played an oncogenic role in ER-positive breast cancer tumorigenesis but also influenced the sensitivity of ER-positive breast cancer cells to tamoxifen. Mechanistically, as an estrogen-responsive gene, MICAL-L2 facilitated the activation of the AKT/mTOR signaling pathway in ER-positive breast cancer cells. Collectively, our findings suggest that MICAL-L2 could serve as a potential prognostic marker for ER-positive breast cancer and represent a promising molecular target for improving endocrine treatment and developing therapeutic approaches for this subtype of breast cancer.
Assuntos
Antineoplásicos Hormonais , Neoplasias da Mama , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Tamoxifeno , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Humanos , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Animais , Estrogênios/farmacologia , Estrogênios/metabolismo , Camundongos Nus , Camundongos , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Células MCF-7 , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/fisiologia , Progressão da Doença , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB CRESUMO
Exploring the effect and mechanism of farmland transfer on agricultural green total factor productivity (AGTFP) in China is of great significance for exerting the effectiveness of China's farmland transfer policy and promoting green agricultural development. Based on panel data from 30 provinces from 2005 to 2020, this paper applies a two-way fixed effects model to analyze the impact of farmland transfer on AGTFP, and the mechanism of farmland transfer on AGTFP is also investigated. We find that farmland transfer has a significant and sound promoting effect on AGTFP, with respect to multiple robustness checks; there is heterogeneity regarding the impact of farmland transfer on AGTFP in terms of food functions, and farmland transfer can promote regional AGTFP through nonagricultural labor transfer and agricultural technology utilization. When considering the fact that farmland transfer has increased China's AGTFP, the Chinese government should continue to adhere to the farmland transfer policy, accelerate nonagricultural labor transfer, improve the level of agricultural technology utilization, and ultimately promote green agricultural development.
