scholarly journals Overexpression of Mucin 1 Suppresses the Therapeutical Efficacy of Disulfiram against Canine Mammary Tumor

Animals ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 37
Author(s):  
Ying Zhao ◽  
Zixiang Lin ◽  
Zhaoyan Lin ◽  
Chaoyu Zhou ◽  
Gang Liu ◽  
...  
Keyword(s):  
Mammary Tumor ◽  
Mammary Tumors ◽  
Expression Level ◽  
Canine Mammary Tumor ◽  
Wild Type ◽  
Mucin 1 ◽  
Mammary Tumor Cell ◽  
Mammary Tumor Cell Line ◽  
Canine Mammary Tumors ◽  
Wild Type Control

Mucin 1 (MUC1), a transmembrane protein, is closely associated with the malignancy and metastasis of canine mammary tumors; however, the role of overexpressed MUC1 in the development of cancer cells and response to drug treatment remains unclear. To address this question, we developed a new canine mammary tumor cell line, CIPp-MUC1, with an elevated expression level of MUC1. In vitro studies showed that CIPp-MUC1 cells are superior in proliferation and migration than wild-type control, which was associated with the upregulation of PI3K, p-Akt, mTOR, Bcl-2. In addition, overexpression of MUC1 in CIPp-MUC1 cells inhibited the suppressing activity of disulfiram on the growth and metastasis of tumor cells, as well as inhibiting the pro-apoptotic effect of disulfiram. In vivo studies, on the other side, showed more rapid tumor growth and stronger resistance to disulfiram treatment in CIPp-MUC1 xenograft mice than in wild-type control. In conclusion, our study demonstrated the importance of MUC1 in affecting the therapeutical efficiency of disulfiram against canine mammary tumors, indicating that the expression level of MUC1 should be considered for clinical use of disulfiram or other drugs targeting PI3K/Akt pathway.

scholarly journals Synergistic growth inhibitory effect of deracoxib with doxorubicin against a canine mammary tumor cell line, CMT-U27

2016 ◽  
Vol 78 (4) ◽  
pp. 657-668 ◽  
Author(s):  
Tülay BAKIREL ◽  
Fulya Üstün ALKAN ◽  
Oya ÜSTÜNER ◽  
Suzan ÇINAR ◽  
Funda YILDIRIM ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Mammary Tumor ◽  
Tumor Cell Line ◽  
Inhibitory Effect ◽  
Canine Mammary Tumor ◽  
Growth Inhibitory Effect ◽  
Mammary Tumor Cell ◽  
Mammary Tumor Cell Line ◽  
Growth Inhibitory

scholarly journals Establishment of 5-Fluorouracil-resistant canine mammary tumor cell line

2017 ◽  
Vol 20 (1) ◽  
pp. 103-110 ◽  
Author(s):  
B. Zhou ◽  
D. Zhang ◽  
S. M. Pei ◽  
H. Zhang ◽  
H. C. Du ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Mammary Tumor ◽  
Tumor Cell Line ◽  
Parental Cell ◽  
Parental Cell Line ◽  
Canine Mammary Tumor ◽  
Mammary Tumor Cell ◽  
Mammary Tumor Cell Line

Abstract Canine mammary tumors are the most common neoplasms in intact female dogs. The surgery cannot always solve the problem, chemotherapy are recommend to these patients. However, chemotherapy could always fail because of multidrug resistance (MDR). Through stepwise increasing 5-Fluorouracil (5-FU) concentration in the culture medium, a 5-FU-resistant canine mammary tumor cell line CMT7364/5-FU was established to disclose the molecular mechanism of the drug resistance. Cell morphology, cell sensitivity to drugs, growth curves, expression of proteins, and chemo-sensitivity in vivo were compared between the parental cell line and resistant cell line. As compared it to its parental cell line (CMT7364), CMT7364/5-FU showed different morphology, cross-resistant to other chemo-drugs and a prolonged population doubling time (PDT). The drug efflux pump proteins (ABCB1 and ABCG2) in CMT7364/5-FU were up-regulated. In vivo, the similar result revealed that CMT7364/5-FU cell line was more resistant to 5-FU. In conclusion, a 5-FU-resistant canine mammary tumor cell line (CMT7364/5-FU) was successfully established, it can serve as a good model for researching the mechanism of MDR and screening effective agents to reverse drug resistance.

Hormonal induction of transfected genes depends on DNA topology

1990 ◽  
Vol 10 (2) ◽  
pp. 625-633
Author(s):  
B Piña ◽  
R J Haché ◽  
J Arnemann ◽  
G Chalepakis ◽  
E P Slater ◽  
...  
Keyword(s):  
Cell Line ◽  
Mammary Tumor ◽  
Binding Sites ◽  
Glucocorticoid Receptors ◽  
Hormone Receptors ◽  
Regulatory Element ◽  
Tumor Cell Line ◽  
Dna Topology ◽  
Mammary Tumor Cell ◽  
Mammary Tumor Cell Line

Plasmids containing the hormone regulatory element of mouse mammary tumor virus linked to the thymidine kinase promoter of herpes simplex virus and the reporter gene chloramphenicol acetyltransferase of Escherichia coli respond to glucocorticoids and progestins when transfected into appropriate cells. In the human mammary tumor cell line T47D, the response to progestins, but not to glucocorticoids, is highly dependent on the topology of the transfected DNA. Although negatively supercoiled plasmids respond optimally to the synthetic progestin R5020, their linearized counterparts exhibit markedly reduced progestin inducibility. This is not due to changes in the efficiency of DNA transfection, since the amount of DNA incorporated into the cell nucleus is not significantly dependent on the initial topology of the plasmids. In contrast, cotransfection experiments with glucocorticoid receptor cDNA in the same cell line show no significant influence of DNA topology on induction by dexamethasone. A similar result was obtained with fibroblasts that contain endogenous glucocorticoid receptors. When the distance between receptor-binding sites or between the binding sites and the promoter was increased, the dependence of progestin induction on DNA topology was more pronounced. In contrast to the original plasmid, these constructs also revealed a similar topological dependence for induction by glucocorticoids. The differential influence of DNA topology is not due to differences in the affinity of the two hormone receptors for DNA of various topologies, but probably reflects an influence of DNA topology on the interaction between different DNA-bound receptor molecules and between receptors and other transcription factors.

Formation of hemidesmosomes in cells of a transformed murine mammary tumor cell line and mechanisms involved in adherence of these cells to laminin and kalinin

1993 ◽  
Vol 106 (4) ◽  
pp. 1083-1102 ◽  
Author(s):  
A. Sonnenberg ◽  
A.A. de Melker ◽  
A.M. Martinez de Velasco ◽  
H. Janssen ◽  
J. Calafat ◽  
...  
Keyword(s):  
Cell Line ◽  
Mammary Tumor ◽  
Cytochalasin B ◽  
Tumor Cell Line ◽  
Metabolic Energy ◽  
Mammary Tumor Cell ◽  
Mammary Tumor Cell Line ◽  
Murine Mammary Tumor ◽  
Integrin Alpha 6 ◽  
In Cells

Keratinocytes attach to an underlying basement membrane by adhesion junctions called hemidesmosomes. We have characterized a cell line, RAC-11P/SD, established from a murine mammary tumor, which differentiates into squamous epithelium and forms well defined hemidesmosomes. These hemidesmosomes contain the integrin alpha 6 beta 4 as well as the hemidesmosomal plaque proteins BP230 and HD1 and are associated with a matrix containing kalinin and laminin. We examined how these cells adhere to laminin and to kalinin present in matrices as well as immunopurified kalinin. We show that adhesion to laminin is energy dependent but does not require an intact actin-containing cytoskeleton. The affinity for kalinin proved to be greater and binding to kalinin was still observed when cells had been treated with deoxyglucose and azide to inhibit metabolic energy. Binding to laminin (or fragment E8), but not to kalinin was partially blocked by a monoclonal antibody specific for the integrin alpha 6 subunit, and only in the initial phase of adhesion. The antibody efficiently blocked adhesion to laminin of cells treated with the microfilament disrupting drug cytochalasin B, but only partially blocked the adhesion of cytochalasin B-treated cells to kalinin, while adherence of cells treated with deoxyglucose and azide to kalinin was blocked completely. The integrin alpha 6 beta 4 is redistributed to the basal surface during adhesion and then is organized into ring-like structures when cells are bound to laminin and localized into hemidesmosomes in cells adhered to kalinin. We suggest that anti-alpha 6 hinders the binding of the alpha 6 beta 4 integrins to its ligands laminin and kalinin, but cannot prevent adhesion when clustering of the integrin has become complete. In addition, there is evidence that adhesion to kalinin is mediated by a second receptor, which associates with the actin-containing cytoskeleton. The presence of such a second receptor is suggested because the cells can spread on kalinin, but not when they have been treated with cytochalasin B. On laminin spreading does not occur, irrespective of whether cells have been treated with cytochalasin B or not. The integrin alpha 3 beta 1, which has been identified as a receptor for kalinin but not for laminin, is strongly expressed in RAC-11P/SD cells and it seems likely that this integrin is responsible for spreading of cells on kalinin.

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