RESUMO
Breast cancer is one of the most common malignant tumors in women. Cell division cycleassociated 5 (CDCA5) is closely associated with the behavior of various cancer types. The aim of the present study was to explore the effect of CDCA5 on breast cancer. Western blot analysis and reverse transcriptionquantitative PCR were used to detect the expression level of CDCA5 in human normal mammary cells and human breast cancer cell lines. To determine its function in MDAMB231 cells, CDCA5 was silenced in MDAMB231 cells by transient short hairpin RNA transfection. Cell Counting Kit8 and clonogenicity assays were used to evaluate cell proliferation. Wound healing and Transwell assays were used to detect cell invasion and migration. Western blot analysis was used to detect the protein expressions of Ki67 and PCNA associated with proliferation, MMP2 and MMP9 associated with migration. CDCA5 was found to be markedly increased in breast cancer cell lines. CDCA5 knockdown was able to suppress cell proliferation, invasion and migration. CDCA5 inhibition downregulated PDS5 cohesinassociated factor A (PDS5A) expression in breast cancer cells. PDS5A overexpression was found to reverse the effect of CDCA5 inhibition on breast cancer cell proliferation and migration. CDCA5 knockdown was shown to suppress the malignant progression of breast cancer cells by regulating PDS5A. The present findings may provide new potential targets for breast cancer therapy.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Neoplasias da Mama , Proteínas de Ciclo Celular , Proteínas Nucleares , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Humanos , Células MCF-7 , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismoRESUMO
Breast cancer (BC), which is widely considered as the most common cancer in women around the world, evokes ~1.7 million new BC cases and 522,000 BC-related deaths each year. Triple negative breast cancer (TNBC) is clinically confirmed as one of the most aggressive subtypes of BC. ORY-1001, a clinically used lysine specific demethylase 1 (LSD1/KDM1A) inhibitor, was investigated herein to confirm its role in the progression of TNBC and reveal the potential mechanism. After treatment with ORY-1001 in MDA-MB-231 and BT549 cells, the cell proliferation and apoptosis were respectively measured by CCK-8 and TUNEL assays. The expression of proliferation- and apoptosis-associated proteins was tested by means of western blot analysis. Then, R1881, an androgen receptor (AR) agonist, was used to evaluate whether the effects of ORY-1001 on proliferation and apoptosis of TNBC cells was mediated by regulating AR. Results indicated that ORY-1001 treatment restrained the proliferation while enhanced the apoptosis of BC cells, accompanied by the change of proliferation- and apoptosis-related proteins expression. Furthermore, ORY-1001 reduced the level of AR in BC cells. After the activation of AR by R1881, the decreased proliferation and enhanced apoptosis of BC cells triggered by ORY-1001 intervention were partially abolished. In conclusion, this paper has presented the first evidence to suggest that ORY-1001 inhibits proliferation and promotes apoptosis of TNBC cells by suppressing AR expression, which may constitute the theoretical basis for the clinical use of ORY-1001 in the treatment of this disease.
Assuntos
Neoplasias de Mama Triplo Negativas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Histona Desmetilases/farmacologia , Humanos , Receptores Androgênicos/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
Dyrk1B, also called minibrain-related kinase (Mirk), is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (Dyrk)/minibrain family of dual-specificity protein kinases. It is a serine/threonine kinase involved in the regulation of tumor progression and cell proliferation. In this study, the role of Dyrk1B in breast cancer development was investigated. The expression of Dyrk1B was detected by Western blot and immunohistochemistry staining, both of which demonstrated that Dyrk1B was overexpressed in breast cancer tissues and cells. Statistical analysis showed that the extent of Dyrk1B expression was associated with multiple clinicopathologic factors, including tumor size, grade, estrogen receptor status, and Ki-67 expression, and that high expression predicted a poor prognosis. The growth of breast cancer cells was inhibited significantly after knockout of DYRK1B by small interfering RNA (siRNA). Moreover, FoxO1 could be phosphorylated by Dyrk1B, and then FoxO1 was shuttled from the cell nucleus into the cytoplasm, which might be the mechanism of Dyrk1B-mediated survival in breast cancer cells. The results suggest that Dyrk1B plays a key role in the progression of breast cancer and provides a new target for breast cancer therapy.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/enzimologia , Proliferação de Células , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Transporte Ativo do Núcleo Celular , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Antígeno Ki-67/metabolismo , Células MCF-7 , Pessoa de Meia-Idade , Gradação de Tumores , Fosforilação , Modelos de Riscos Proporcionais , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Interferência de RNA , Receptores de Estrogênio/metabolismo , Fatores de Tempo , Transfecção , Carga Tumoral , Regulação para Cima , Quinases DyrkRESUMO
BACKGROUND AND AIMS: We undertook this study to investigate the influence of PIRH2 (p53-induced RING-H2) protein on the proliferation and cell cycle of breast cancer cell lines. METHODS: PIRH2 expression was detected by Western blot analysis, immunohistochemistry (IHC) and Kaplan-Meier curve analysis. Cell proliferation was assessed by cell counting kit-8 (CCK-8). Cell cycle control was analyzed by flow cytometry. RESULTS: PIRH2 was up-regulated in breast cancer tissues and cell lines and up-regulated PIRH2 was highly associated with tumor size, grade, ER, and Ki-67. Moreover, Kaplan-Meier curve showed that up-regulated PIRH2 was related to the poor overall survival of patients with breast carcinoma. When the expression of PIRH2 was inhibited by siRNA transfection, cell proliferation was reduced. In addition, the number of G0/G1 phase cells was increased, but G2/M cells were not affected significantly. CONCLUSION: Decrease of PIRH2 expression in the breast cancer cell line MDA-MB-231 resulted in reduced tumor cell growth via the inhibition of cell proliferation and the interruption of cell cycle transition.