Intercellular interactions and progression of hormonal resistance of breast cancer cells

Semina, Svetlana E.; Bagrov, Dmitry; Красильников, М. А.

doi:10.17650/2313-805x.2015.2.2.50-55

Cited by 2 publications

(1 citation statement)

References 18 publications

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“…Experiments were performed on the in-vitro-cultured oestrogen-dependent MCF7 cells and tamoxifen-resistant MCF7/T subline obtained by long-term tamoxifen treatment of the parent cells. Earlier we have shown that long-term treatment of the MCF7 cells with the exosomes from the resistant MCF7/T cells results in the development of tamoxifen resistance in the recipient cells [71]. To further the study of the mechanism of the exosome-induced resistance, the profile of exosomal miRNAs was analysed.…”

Section: Resultsmentioning

confidence: 99%

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

et al. 2021

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Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the activity or synthesis of hormone receptors), or by activation of oestrogen-independent signalling pathways. Recently the effect of exosome-mediated intercellular transfer of hormonal resistance was revealed, however, the molecular mechanism of this effect is still unknown. Here, the role of exosomal miRNAs (microRNAs) in the transferring of hormonal resistance in breast cancer cells has been studied. The methods used in the work include extraction, purification and RNAseq of miRNAs, transfection of miRNA mimetics, immunoblotting, reporter analysis and the MTT test. Using MCF7 breast cancer cells and MCF7/T tamoxifen-resistant sub-line, we have found that some miRNAs, suppressors of oestrogen receptor signalling, are overexpressed in the exosomes of the resistant breast cancer cells. The multiple (but not single) transfection of one of the identified miRNA, miR-181a-2, into oestrogen-dependent MCF7 cells induced the irreversible tamoxifen resistance associated with the continuous block of the oestrogen receptor signalling and the activation of PI3K/Akt pathway. We suppose that the miRNAs-ERα suppressors may act as trigger agents inducing the block of oestrogen receptor signalling and breast cancer cell transition to an aggressive oestrogen-independent state.

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Section: Resultsmentioning

confidence: 99%

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

et al. 2021

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LYN kinase and estrogen receptor ERα: involvement in carcinogenesis and potential therapeutic target for tumors

2021

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Primary or secondary resistance is an important problem when treating any type of tumor. It is often associated with changes in target genes’ functioning. This raises the question of understanding functional intracellular interactions of genes and proteins in oncological processes and therapeutic resistance occurring. When searching target proteins of targeted therapy, it is necessary to identify biomolecules, participating in cell signaling life, which differ significantly in normal and oncological processes and interact with a large number of pathways. It is also important that these biomolecules are not an artifact of tumor therapy or cell line cultivation, and that it is possible to influence them directly, obtaining complex effect. In addition, it is important to study changes occurring during therapy with the biomolecules, which include proto-oncogene of SRC family kinase LYN and gene of the estrogen receptor α ESR1. All these factors may help to overcome the emerging resistance.Objective – to study the way genes of SRC kinase LYN and estrogen receptor α ESR1 influence oncological processes and occurrence of therapeutic resistance.

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Intercellular interactions and progression of hormonal resistance of breast cancer cells

Cited by 2 publications

References 18 publications

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

LYN kinase and estrogen receptor ERα: involvement in carcinogenesis and potential therapeutic target for tumors

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