Document Type : Original Article
Authors
1 Department of Biology, Ars. C., Islamic Azad University, Arsanjan, Iran
2 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
3 Department of Biology, Faculty of Science, Shahid Bahonar University of Kerman, Kerman, Iran
Abstract
Introduction: Male breast cancer (MBC) is a rare disease with a poorer prognosis compared to females, largely due to late-stage diagnosis and the absence of specific treatment protocols. Transcriptome studies have greatly facilitated the evaluation of genes and pathways involved in cancer and the discovery of biomarkers by enabling the simultaneous assessment of all mRNAs present in a sample. In this study, we investigated transcriptomic changes in MBC tumor cells in response to tamoxifen to identify key genes and pathways involved.
Methods: A CD44+/CD24- cancer-cell-enriched population was confirmed by flow cytometry. Cells were treated with 100 μM tamoxifen for 48 hours alongside untreated controls, and whole-transcriptome RNA sequencing was performed by Illumina NovaSeq 6000 (Novogene, England). Differentially expressed genes (DEGs) were extracted by edgeR package. Gene Ontology and pathway analysis were performed by enrichR package. qRT-PCR was performed for validation of RNA-seq results.
Results: Differential expression analysis identified 54 differentially expressed genes following tamoxifen exposure. Gene Ontology, KEGG, Reactome and MSigDB Hallmark enrichment analyses revealed a dominant signature of mitotic cell cycle, chromosome segregation and spindle organization processes. Four candidate genes spanning distinct functional clusters (CCNB1, KIF11, LARS2, COL14A1) were selected for qRT-PCR validation against the same cell line and against MCF-7 cells, an ER+/HER2- line with a comparable receptor profile.
Conclusions: This study provides, to our knowledge, one of the first transcriptome-level characterizations of a patient-derived primary MBC culture under tamoxifen exposure, and highlights cell-cycle-related transcripts as candidate markers of endocrine response in MBC.
Highlights
Koorosh Poormahmoodian (PubMed) (Google Scholar)
Saeideh Jafarinejad-Farsangi (PubMed) (Google Scholar)
Leila Kohan (PubMed) (Google Scholar)
Sara Soltanian (PubMed) (Google Scholar)
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