Purpose: Multidrug resistance (MDR) is resistance to wide range of structurally unrelated anticancer agents. MDR is a serious limitation to the effective chemotherapy. Involvement of ETS1 overexpression in upregulation of MDR1 gene expression is implicated. In the present study the aim was to assess the involvement of ETS1 and the genes, which encode the proteins interacting with ETS1 in drug resistant MCF-7 breast cancer cells.
Methods: Drug resistant sublines to paclitaxel (MCF-7/Pac), docetaxel (MCF-7Doc), vincristine (MCF-7/Vinc) and doxorubicin (MCF-7/Dox) that were developed from sensitive MCF-7 cells (MCF-7/S) were used. cDNA microarray analysis was performed for the RNA samples of sensitive and resistant cells in duplicate experiments. GeneSpring GX 7.3.1 Software was used in data analysis. Microarray data was supported by immunocytochemistry and western blot for drug resistance protein, P-gp, encoded by MDR1 gene.
Results: According to microarray data MDR1 and ETS1 genes were highly overexpressed in all of the resistant sublines. Matrix metalloproteinase-1 gene (MMP-1) was also tremendously upregulated only in vincristine resistant cells. Immunocytochemistry and western blot results confirmed that P-gp was highly overexpressed in resistant sublines compared to original MCF-7 cells.
Conclusion: High ETS1 expression levels in all resistant MCF-7 sublines may lead to the upregulation of the transcription of MDR1 gene. Overexpression of ETS1 gene in resistant cells may have contributed to the development of resistance in the cells. Furthermore, the significant upregulation of MMP1 and MMP9 in MCF-7/Vinc may also be related to an acquired invasive behavior of MCF-7 cell line due to vincristine treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.biopha.2010.01.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.
Proc Natl Acad Sci U S A
January 2025
Cancer Biology & Genetics Program, Sloan Kettering Institute, New York, NY 10065.
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.
View Article and Find Full Text PDFComputational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody-drug conjugates.
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFAnti-Mycobacterial Activity of Bacterial Topoisomerase Inhibitors with Dioxygenated Linkers.
ACS Infect Dis
January 2025
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523, United States.
Developing new classes of drugs that are active against infections caused by is a priority for treating and managing this deadly disease. Here, we describe screening a small library of 20 DNA gyrase inhibitors and identifying new lead compounds. Three structurally diverse analogues were identified with minimal inhibitory concentrations of 0.
View Article and Find Full Text PDFBackground: The lives of adolescents and young people living with HIV (LHIV) are dominated by complex psychological and social stressors. These may be more pronounced among those perinatally infected. This longitudinal mixed-methods study describes the clinical and psychosocial challenges faced by HIV perinatally infected young mothers in Harare, Zimbabwe to inform tailored support.
View Article and Find Full Text PDFDisseminated organ and tissue infection secondary to carbapenem-resistant Klebsiella pneumoniae bloodstream infection for acute lymphoblastic leukemia treated with ceftazidime-avibactam: Two case reports.
Medicine (Baltimore)
January 2025
Department of Hematology, Tongde Hospital of Zhejiang Province, Hangzhou, P.R. China.
Rationale: Carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections are a severe complication resulting from granulocyte deficiency following chemotherapy for hematologic malignancies and have a high mortality rate. However, reports of disseminated organ infections secondary to bloodstream infections are rare.
Patient Concerns And Diagnoses: We report 2 cases of patients with acute lymphoblastic leukemia who both developed CRKP bloodstream infections during the granulocyte deficiency stage following chemotherapy, with 1 case of secondary bacterial liver abscess and 1 case of secondary septic arthritis.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!