Transcriptome profiling identified differentially expressed genes and pathways associated with tamoxifen resistance in human breast cancer

The BK polyomavirus is both the cause of nephropathy in kidney transplant patients (1-3) and one of many viruses whose presence has previously been investigated in the tumors of patients with breast cancer (4, 5). We mined published microarray data (6, 7) to identify differentially expressed genes associated with BK polyomavirus infection of the kidneys in patients with transplant-associated nephropathy, integrating these findings with whole transcriptome analysis of human breast cancers to determine the presence of differentially expressed genes in breast cancers whose expression was significantly modulated by BK virus infection. We identified conserved transcriptional modulation of the IGF-like family receptor 1 (IGFLR1) and the proteasome subunit 9 (PSMB9) in the kidneys of patients with transplant-associated nephropathy and in the primary tumors of patients with breast cancer. These data demonstrate the existence of common transcriptional modulation in human breast cancer and in the kidneys associated with BK virus, and provide rationale for evaluation of BK virus large T-antigen expression in the human breast during breast cancer.

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A shared transcriptional landscape between human breast cancers and breast cancers induced by genetic modeling of viral infection in mice.

10.31219/osf.io/8uzcq ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Viral Infection ◽

Differentially Expressed Genes ◽

Mammary Tumor ◽

Human Breast Cancer ◽

Differentially Expressed ◽

Breast Cancers ◽

Human Breast ◽

Transgenic Expression ◽

Genetic Modeling

We recently demonstrated, through analysis of published transcriptome data from human and murine breast cancer that eight genes whose expression was most different in tumors that arise in the mouse breast following transgenic expression of the SV40 large T-antigen or modeling of integration following infection with multiple mammary tumor viruses, including CD36, ASPM, PDGFD and CEP55 were also among the genes most differentially expressed in the primary tumors of humans with breast cancer (1). We report here that these transcriptional similarities are a much larger phenomena, with 45-54% of the top one hundred most differentially expressed genes in murine breast cancer resulting from genetic modeling of viral infection with the murine mammary tumor virus MMTV or transgenic expression of SV40 large T also among the most differentially expressed genes in human breast cancer. Despite inherent differences in transcription due to species divergence, blind whole transcriptome (2-4) analyses reveals striking transcriptional similarity in the landscape of human breast cancer and murine breast cancers resulting from genetic modeling of viral infection, providing further evidence to support the hypothesis that one or more viral agents with transformation capacity may contribute to the development of human breast cancer.

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