Transcriptomic profile of trastuzumab-resistant breast cancer cell line BT-474

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Resumo

The development of resistance to trastuzumab in HER2-positive breast cancer is a serious clinical problem that limits the effectiveness of targeted therapy. In a significant proportion of patients, the mechanisms of resistance development remain poorly understood. The BT-474 cell line was selected as an optimal model for the study because it represents a HER2-positive luminal B subtype breast cancer cell line. To identify molecular mechanisms of resistance, a comprehensive transcriptomic analysis based on RNA-seq data comparison of three independent datasets including both sensitive and trastuzumab-resistant variants was applied. The methodological approach included multi-step bioinformatics analysis followed by identification of regulatory interactions. The study identified genes with increased expression (FUCA2, HSPE1, SHLD1, NMD3) and genes with decreased expression (GPC5, FSTL1, ATG16L2, POLD2) in resistant cells. Key transcription factors (E2F1, MYC, YBX1, HEY1, NFIC, TFAP2A, AP-1/JUN, NCOA1) regulating the expression of the detected genes during resistance development were identified. The identified changes indicate a complex reprogramming of transcriptional activity affecting cell cycle processes, DNA repair, metabolism, and epithelial-mesenchymal transition. The findings expand the understanding of the molecular mechanisms of trastuzumab resistance and open prospects for the development of novel therapeutic strategies to overcome drug resistance in HER2-positive breast cancer.

Sobre autores

S. Shifon

Novosibirsk National Research State University

Email: s.shsherbakova@g.nsu.ru
Novosibirsk, 630090 Russia

I. Karpets

Novosibirsk National Research State University

Novosibirsk, 630090 Russia

A. Chesnokova

Novosibirsk National Research State University

Novosibirsk, 630090 Russia

P. Karitskaya

Novosibirsk National Research State University

Novosibirsk, 630090 Russia

E. Ukladov

Novosibirsk National Research State University

Novosibirsk, 630090 Russia

I. Evgenov

Novosibirsk National Research State University

Novosibirsk, 630090 Russia

S. Sidorov

Novosibirsk National Research State University; City Clinical Hospital No. 1

Novosibirsk, 630090 Russia; Novosibirsk, 630047 Russia

L. Gulyaeva

Novosibirsk National Research State University; Research Institute of Molecular Biology and Biophysics

Email: lfgulyaeva@gmail.com
Novosibirsk, 630090 Russia; Novosibirsk, 630060 Russia

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