Transcriptomic Profiling Identifies Differentially Expressed Genes in Palbociclib-Resistant ER+ MCF7 Breast Cancer Cells

• Published in: Genes Vol. 11; no. 4; p. 467
• Main Authors: Lanceta, Lilibeth, O'Neill, Conor, Lypova, Nadiia, Li, Xiahong, Rouchka, Eric, Waigel, Sabine, Gomez-Gutierrez, Jorge G, Chesney, Jason, Imbert-Fernandez, Yoannis
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24-04-2020; MDPI
• Subjects: Antineoplastic Agents - pharmacology; Autophagy; Biomarkers, Tumor - genetics; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell cycle; Computational Biology; Cyclin-dependent kinase 4; Cyclin-dependent kinases; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA damage; DNA repair; Drug Resistance, Neoplasm - genetics; Endocrine therapy; Estrogen receptors; Female; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Genomes; Humans; Kinases; Metabolic pathways; Metastasis; Phagocytosis; Piperazines - pharmacology; Proteins; Pyridines - pharmacology; Receptors, Estrogen - metabolism; Ribonucleic acid; RNA; Transcriptome - drug effects; Transcriptomics; Tumor Cells, Cultured; Tumors; metabolic rewiring; CDK4/6; estrogen receptor; CDK4/6 inhibitors; breast cancer; DNA repair; palbociclib; therapy resistance
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes11040467

Acquired resistance to cyclin-dependent kinases 4 and 6 (CDK4/6) inhibition in estrogen receptor-positive (ER+) breast cancer remains a significant clinical challenge. Efforts to uncover the mechanisms underlying resistance are needed to establish clinically actionable targets effective against resistant tumors. In this study, we sought to identify differentially expressed genes (DEGs) associated with acquired resistance to palbociclib in ER+ breast cancer. We performed next-generation transcriptomic RNA sequencing (RNA-seq) and pathway analysis in ER+ MCF7 palbociclib-sensitive (MCF7/pS) and MCF7 palbociclib-resistant (MCF7/pR) cells. We identified 2183 up-regulated and 1548 down-regulated transcripts in MCF7/pR compared to MCF7/pS cells. Functional analysis of the DEGs using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database identified several pathways associated with breast cancer, including 'cell cycle', 'DNA replication', 'DNA repair' and 'autophagy'. Additionally, Ingenuity Pathway Analysis (IPA) revealed that resistance to palbociclib is closely associated with deregulation of several key canonical and metabolic pathways. Further studies are needed to determine the utility of these DEGs and pathways as therapeutics targets against ER+ palbociclib-resistant breast cancer.