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Registration Number

0224U032933, (0124U004351) , R & D reports

Title

Elucidation of functional relationships between isoforms of estrogen receptor ERα and isoforms of ribosomal protein kinase S6 (S6K1) in human breast carcinoma cells of different molecular subtypes

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Cтворення та характеристика модельних субліній клітин карциноми грудної залози людини ліній MCF-7 та MDA-MB 231 з диференційною експресією ізоформ ERα та S6K1

Head

Filonenko Valerii V., Доктор біологічних наук

Registration Date

11-12-2024

Organization

Institute of Molecular Biology and Genetics of NAS of Ukraine

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The goal of the project is to determine the molecular regulatory relationships between isoforms of the estrogen receptor ERα and S6K1 kinase in human breast carcinoma cells of different molecular subtypes at the levels of regulation of their expression and activity and evaluate their role in the regulation of the transcriptome of genes associated with tumor progression, manifestations of key features of malignant cells and the effectiveness of tumor formation and metastases in model animals

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Breast cancer ranks first among oncological diseases in terms of mortality among women worldwide. The vast majority of malignant breast tumors are ER+ (according to various estimates, up to 70%), which indicates the dependence of tumor progression on estrogens. In clinical practice, the most widely used is antiestrogen therapy aimed at both blocking hormone synthesis and inhibiting estrogen receptor activity/expression. However, in a third of cases, tumors are insensitive to such therapy, or over time acquire such resistance. One of the reasons for resistance is considered to be the activity of cell signaling systems. In particular, with the participation of mTOR/S6K1-dependent signaling, estrogen-independent activation of ERα can be induced by S6K1-mediated phosphorylation of ERα at Ser167. On the other hand, the extremely important functional role of mTOR/S6K1-dependent signaling in the progression of breast tumors is recognized, therefore, in clinical practice, in cases of ER+ tumors with signs of metastasis, in addition to antiestrogen therapy, its use in combination with mTOR inhibitors is approved. Given the wide range of regulatory mTOR/S6K1-controlled processes in the cell, such therapy has quite severe side effects and therefore there is a need to find narrow links of influence on mTOR/S6K1 signaling and ERα activity. Elucidation of the subtle regulatory relationships that exist between ERα and the mTOR/S6K1 signaling cascade in RGH cells of different molecular subtypes is extremely relevant. The goal of the project is to elucidate the molecular regulatory relationships between estrogen receptor ERα isoforms and S6K1 kinase in human breast carcinoma cells of different molecular subtypes at the levels of expression and activity regulation and to determine their role in regulating the transcriptome of genes associated with tumor progression, manifestations of key features of malignant cells, and the efficiency of tumor formation and metastasis in animals.

Product Description

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Harifulin Oleh M.
Krupska Iryna V.
Martsyniuk Marko Ye.
Palchevskyi Serhii S.
Savinska Liliia O.
Yatsenko Mykola V.

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2024-12-11