scholarly journals c-myc regulates the sensitivity of breast cancer cells to palbociclib via c-myc/miR-29b-3p/CDK6 axis

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Wenfei Ji ◽  
Wenwen Zhang ◽  
Xin Wang ◽  
Yaqin Shi ◽  
Fang Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Xenograft Model ◽  
Metastatic Breast ◽  
Cancer Cell Lines ◽  
The Cancer Genome Atlas ◽  
Tumor Xenograft ◽  
Breast Cancer Cell Lines

Abstract Palbociclib, a CDK4/6 inhibitor, has been granted accelerated approval by US FDA for hormone receptor-positive HER2-negative metastatic breast cancer. To determine potential biomarkers of palbociclib sensitivity to assist in patient selection and clinical development, we investigated the effects of palbociclib in a panel of molecularly characterized breast cancer cell lines. We quantified palbociclib sensitivity and c-myc expression in 11 breast cancer cell lines, 124 breast cancer samples, and The Cancer Genome Atlas database. We found non-TNBC subtypes were more sensitive to palbociclib than TNBC. Activation of c-myc led to differential palbociclib sensitivities, and further inhibition of c-myc enhanced palbociclib sensitivity. Moreover, we identified for the first time a c-myc/miR-29b-3p/CDK6 axis in breast cancer that could be responsible for c-myc-induced palbociclib insensitivity, in which c-myc activation resulted in downregulation of miR-29b-3p, further activated CDK6 and inhibited cell-cycle arrest at G1 phase. Moreover, downregulated (inactived) c-myc-induced oncogenic addiction could increase palbociclib efficacy, using both Xenograft model and patient-derived tumor xenograft (PDTX) model. Our finding extends the concept of combined blockade of the CDK4/6 and c-myc signaling pathways to increase palbociclib sensitivity, making c-myc a promising biomarker for palbociclib sensitivity in breast cancer.

scholarly journals The Synergistic Effects of SHR6390 Combined With Pyrotinib on HER2+/HR+ Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yukun Wang ◽  
Xiang Yuan ◽  
Jing Li ◽  
Zhiwei Liu ◽  
Xinyang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Molecular Mechanisms ◽  
Xenograft Model ◽  
Cancer Cell Lines ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

HER2+/HR+ breast cancer is a special molecular type of breast cancer. Existing treatment methods are prone to resistance; “precision treatment” is necessary. Pyrotinib is a pan-her kinase inhibitor that can be used in HER2-positive tumors, while SHR6390 is a CDK4/6 inhibitor that can inhibit ER+ breast cancer cell cycle progression and cancer cell proliferation. In cancer cells, HER2 and CDK4/6 signaling pathways could be nonredundant; co-inhibition of both pathways by combination of SHR6390 and pyrotinib may have synergistic anticancer activity on HER2+/HR+ breast cancer. In this study, we determined the synergy of the two-drug combination and underlying molecular mechanisms. We showed that the combination of SHR6390 and pyrotinib synergistically inhibited the proliferation, migration, and invasion of HER2+/HR+ breast cancer cells in vitro. The combination of two drugs induced G1/S phase arrest and apoptosis in HER2+/HR+ breast cancer cell lines. The combination of two drugs prolonged the time to tumor recurrence in the xenograft model system. By second-generation RNA sequencing technology and enrichment analysis of the pyrotinib-resistant cell line, we found that FOXM1 was associated with induced resistance to HER2-targeted therapy. In HER2+/HR+ breast cancer cell lines, the combination of the two drugs could further reduce FOXM1 phosphorylation, thereby enhancing the antitumor effect to a certain extent. These findings suggest that SHR6390 combination with pyrotinib suppresses the proliferation, migration, and invasion of HER2+/HR+ breast cancers through regulation of FOXM1.

UBE2T knockdown inhibits cell growth and metastasis of breast cancer through Wnt/β-catenin pathway

2021 ◽  
Author(s):  
Tao Xueqin ◽  
Mei Jinhong ◽  
Huang Yuping
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Cell Lines ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Mesenchymal Transition

Abstract Background: Emerging evidences have demonstrated that Ubiquitin-conjugating enzyme E2T (UBE2T) is dysregulated and play critical roles in various cancers. With the development of sequencing technology, studies have discovered that UBE2T is overexpressed in breast cancer tissues. However, the biological roles of UBE2T in breast cancer are still far to clear. In the present study, Methods: We analyzed the UBE2T expression in the Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess the expression of UBE2T in breast cancer cell lines. Cell proliferation, invasion and epithelial-mesenchymal transition (EMT) were determined by using CCK-8, EdU, Transwell and western blot assays.Results: UBE2T was highly expressed in breast cancer cell lines. Functional analysis revealed that silence or elevation of UBE2T inhibited or promoted the proliferation, migration, invasion and EMT and Wnt/β-catenin signaling pathway related markers of MCF-7 cells. Mechanically, blocking of Wnt/β-catenin pathway by XAV939 reversed the promotion effect of UBE2T overexpression on breast cancer cells’ proliferation, migration and invasion.Conclusion: Our findings emphasized that UBE2T may act as an oncogene via activating the Wnt/β-catenin pathway, which may provide a potential therapeutic target for the treatment of breast cancer.

scholarly journals INHBA Promotes Cell Proliferation and Metastasis of Breast Cancer through Wnt/β-catenin Signaling Pathway

2021 ◽  
Author(s):  
Tao Xueqin ◽  
Mei Jinhong ◽  
Huang Yuping
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
The Cancer Genome Atlas ◽  
Breast Cancer Cell Lines ◽  
Mesenchymal Transition

Abstract BackgroundEmerging evidences have demonstrated that inhibin subunit beta A (INHBA) is dysregulated and play critical roles in various cancers. With the development of sequencing technology, studies have discovered that INHBA is overexpressed in breast cancer tissues. However, the biological roles of INHBA in breast cancer are still far to clear. In the present study, MethodsWe analyzed the INHBA expression in the Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess the expression of INHBA in breast cancer cell lines. Cell proliferation, invasion and epithelial-mesenchymal transition (EMT) were determined by using CCK-8, EdU, Transwell and western blot assays.ResultsINHBA was highly expressed in breast cancer cell lines. Functional analysis revealed that silence or elevation of INHBA inhibited or promoted the proliferation, migration, invasion and EMT and Wnt/β-catenin signaling pathway related markers of MCF-7 cells. Mechanically, blocking of Wnt/β-catenin pathway by XAV939 reversed the promotion effect of INHBA overexpression on breast cancer cells’ proliferation, migration and invasion.ConclusionOur findings emphasized that INHBA may act as an oncogene via activating the Wnt/β-catenin pathway, which may provide a potential therapeutic target for the treatment of breast cancer.

scholarly journals APOBEC3B expression in breast cancer cell lines and tumors depends on the estrogen receptor status

2020 ◽  
Vol 41 (8) ◽  
pp. 1030-1037 ◽  
Author(s):  
Krizia-Ivana Udquim ◽  
Clara Zettelmeyer ◽  
A Rouf Banday ◽  
Seraph Han-Yin Lin ◽  
Ludmila Prokunina-Olsson
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mutagenic Activity ◽  
Breast Tumors ◽  
Cancer Cell Lines ◽  
The Cancer Genome Atlas ◽  
Breast Cancer Cell Lines

Abstract Increased exposure to estrogen is associated with an elevated risk of breast cancer. Considering estrogen as a possible mutagen, we hypothesized that exposure to estrogen alone or in combination with the DNA-damaging chemotherapy drug, cisplatin, could induce expression of genes encoding enzymes involved in APOBEC-mediated mutagenesis. To test this hypothesis, we measured the expression of APOBEC3A (A3A) and APOBEC3B (A3B) genes in two breast cancer cell lines treated with estradiol, cisplatin or their combination. These cell lines, T-47D (ER+) and MDA-MB-231 (ER−), differed by the status of the estrogen receptor (ER). Expression of A3A was not detectable in any conditions tested, while A3B expression was induced by treatment with cisplatin and estradiol in ER+ cells but was not affected by estradiol in ER− cells. In The Cancer Genome Atlas, expression of A3B was significantly associated with genotypes of a regulatory germline variant rs17000526 upstream of the APOBEC3 cluster in 116 ER− breast tumors (P = 0.006) but not in 387 ER+ tumors (P = 0.48). In conclusion, we show that in breast cancer cell lines, A3B expression was induced by estradiol in ER+ cells and by cisplatin regardless of ER status. In ER+ breast tumors, the effect of estrogen may be masking the association of rs17000526 with A3B expression, which was apparent in ER− tumors. Our results provide new insights into the differential etiology of ER+ and ER− breast cancer and the possible role of A3B in this process through a mitogenic rather than the mutagenic activity of estrogen.

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