scholarly journals PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes

2017 ◽  
Vol 38 (10) ◽  
pp. 966-975 ◽  
Author(s):  
Deepak K Singh ◽  
Omid Gholamalamdari ◽  
Mahdieh Jadaliha ◽  
Xiao Ling Li ◽  
Yo-Chuen Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Cycle Genes

scholarly journals Overexpression of β-Arrestins inhibits proliferation and motility in triple negative breast cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saber Yari Bostanabad ◽  
Senem Noyan ◽  
Bala Gur Dedeoglu ◽  
Hakan Gurdal
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cell Function ◽  
Expression Profiles ◽  
Tissue Samples ◽  
Expression Levels ◽  
Cell Cycle Genes

Abstractβ-Arrestins (βArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of βArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of βArrs. Our approach examines the direct influence of βArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of βArr1 or βArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of βArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of βArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that βArr1 and βArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.

scholarly journals Treatment with DHA Modifies the Response of MDA-MB-231 Breast Cancer Cells and Tumors from nu/nu Mice to Doxorubicin through Apoptosis and Cell Cycle Arrest

2019 ◽  
Vol 149 (1) ◽  
pp. 46-56 ◽  
Author(s):  
Marnie Newell ◽  
Miranda Brun ◽  
Catherine J Field
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cyclin B1 ◽  
Cell Cycle Genes ◽  
Cycle Arrest ◽  
And Function

ABSTRACT Background Docosahexaenoic acid (DHA) has been shown to reduce growth of breast cancer cells in vitro and in vivo; it may also benefit the action of cytotoxic cancer drugs. The mechanisms for these observations are not completely understood. Objectives We sought to explore how pretreatment of MDA-MB-231 breast cancer cells with DHA alters gene expression with doxorubicin (DOX) treatment and confirm that feeding DHA to tumor-bearing nu/nu mice improves the efficacy of DOX. Methods MDA-MB-231 cells were subjected to 4 conditions: a control mixture of 40 μM linoleic and 40 μM oleic acid (OALA), DHA (60 μM plus OALA), OALA DOX (0.41 μM), or DHA DOX (plus OALA) and assessed for effects on viability and function. Female nu/nu mice (6 wk old) bearing MDA-MB-231 tumors were randomly assigned to a nutritionally complete diet (20 g ± 2.8 g DHA/100 g diet) containing a polyunsaturated:saturated fat ratio of 0.5, with or without injections 2 times/wk of 5 mg DOX/kg for 4 wk. Results Microarray and protein analysis indicated that DHA DOX cells, compared with OALA DOX, had upregulated expression of apoptosis genes, Caspase-10 (1.3-fold), Caspase-9 (1.4-fold), and Receptor (TNFRSF)-interacting serine-threonine kinase 1 (RIPK1) (1.2-fold), while downregulating cell cycle genes, Cyclin B1 (−2.1-fold), WEE1 (−1.6-fold), and cell division cycle 25 homolog C (CDC25C) (−1.8-fold) (P < 0.05). DHA DOX–treated mice had 50% smaller tumors than control mice (P < 0.05). Analysis of proapoptotic proteins from tumors of DHA DOX mice showed increased Caspase-10 (by 68%) and BH3 interacting domain death agonist (Bid) (by 50%), decreased B-cell CLL/lymphoma 2 (BCL2) (by 24%), and decreased cell cycle proteins Cyclin B1 and Cdc25c (both by 42%), compared with control mice (P < 0.05). Conclusions Supplementation with DHA facilitates the action of DOX in MDA-MB-231 cells and in nu/nu mice, which may occur via amplification of the effect of DOX on apoptosis and cell cycle genes.

scholarly journals Matrix degradation and cell proliferation are coupled to promote invasion and escape from an engineered human breast microtumor

2021 ◽  
Vol 13 (1) ◽  
pp. 17-29
Author(s):  
Emann M Rabie ◽  
Sherry X Zhang ◽  
Andreas P Kourouklis ◽  
A Nihan Kilinc ◽  
Allison K Simi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Type I ◽  
Matrix Degradation ◽  
Human Breast ◽  
Rate Of Invasion

Abstract Metastasis, the leading cause of mortality in cancer patients, depends upon the ability of cancer cells to invade into the extracellular matrix that surrounds the primary tumor and to escape into the vasculature. To investigate the features of the microenvironment that regulate invasion and escape, we generated solid microtumors of MDA-MB-231 human breast carcinoma cells within gels of type I collagen. The microtumors were formed at defined distances adjacent to an empty cavity, which served as an artificial vessel into which the constituent tumor cells could escape. To define the relative contributions of matrix degradation and cell proliferation on invasion and escape, we used pharmacological approaches to block the activity of matrix metalloproteinases (MMPs) or to arrest the cell cycle. We found that blocking MMP activity prevents both invasion and escape of the breast cancer cells. Surprisingly, blocking proliferation increases the rate of invasion but has no effect on that of escape. We found that arresting the cell cycle increases the expression of MMPs, consistent with the increased rate of invasion. To gain additional insight into the role of cell proliferation in the invasion process, we generated microtumors from cells that express the fluorescent ubiquitination-based cell cycle indicator. We found that the cells that initiate invasions are preferentially quiescent, whereas cell proliferation is associated with the extension of invasions. These data suggest that matrix degradation and cell proliferation are coupled during the invasion and escape of human breast cancer cells and highlight the critical role of matrix proteolysis in governing tumor phenotype.

scholarly journals Mutant p53L194F Harboring Luminal-A Breast Cancer Cells Are Refractory to Apoptosis and Cell Cycle Arrest in Response to MortaparibPlus, a Multimodal Small Molecule Inhibitor

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3043
Author(s):  
Ahmed Elwakeel ◽  
Anissa Nofita Sari ◽  
Jaspreet Kaur Dhanjal ◽  
Hazna Noor Meidinna ◽  
Durai Sundar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Small Molecule ◽  
Breast Cancer Cells ◽  
Luminal A ◽  
Molecular Analyses ◽  
Cycle Arrest ◽  
Mcf 7

We previously performed a drug screening to identify a potential inhibitor of mortalin–p53 interaction. In four rounds of screenings based on the shift in mortalin immunostaining pattern from perinuclear to pan-cytoplasmic and nuclear enrichment of p53, we had identified MortaparibPlus (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole) as a novel synthetic small molecule. In order to validate its activity and mechanism of action, we recruited Luminal-A breast cancer cells, MCF-7 (p53wild type) and T47D (p53L194F) and performed extensive biochemical and immunocytochemical analyses. Molecular analyses revealed that MortaparibPlus is capable of abrogating mortalin–p53 interaction in both MCF-7 and T47D cells. Intriguingly, upregulation of transcriptional activation function of p53 (as marked by upregulation of the p53 effector gene—p21WAF1—responsible for cell cycle arrest and apoptosis) was recorded only in MortaparibPlus-treated MCF-7 cells. On the other hand, MortaparibPlus-treated T47D cells exhibited hyperactivation of PARP1 (accumulation of PAR polymer and decrease in ATP levels) as a possible non-p53 tumor suppression program. However, these cells did not show full signs of either apoptosis or PAR-Thanatos. Molecular analyses attributed such a response to the inability of MortaparibPlus to disrupt the AIF–mortalin complexes; hence, AIF did not translocate to the nucleus to induce chromatinolysis and DNA degradation. These data suggested that the cancer cells possessing enriched levels of such complexes may not respond to MortaparibPlus. Taken together, we report the multimodal anticancer potential of MortaparibPlus that warrants further attention in laboratory and clinical studies.

Steroidal aromatase inhibitors inhibit growth of hormone-dependent breast cancer cells by inducing cell cycle arrest and apoptosis

APOPTOSIS ◽  
2013 ◽  
Vol 18 (11) ◽  
pp. 1426-1436 ◽  
Author(s):  
Cristina Amaral ◽  
Carla Varela ◽  
Margarida Borges ◽  
Elisiário Tavares da Silva ◽  
Fernanda M. F. Roleira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Aromatase Inhibitors ◽  
Breast Cancer Cells ◽  
Cycle Arrest ◽  
Steroidal Aromatase Inhibitors
Sign in / Sign up

Export Citation Format

Share Document