ArticleBreast cancer research and treatment2014
Inhibition of LINE-1 retrotransposon-encoded reverse transcriptase modulates the expression of cell differentiation genes in breast cancer cells.
Article in Breast cancer research and treatment, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- A Systematic Review of Expression and Immunogenicity of Human Endogenous Retroviral Proteins in Cancer and Discussion of Therapeutic Approaches.International journal of molecular sciences · 2022Pooled it
- The therapeutic potential of transposable element activity modulation.EMBO molecular medicine · 2026Review
- Approaches to repurposing reverse transcriptase antivirals in cancer.British journal of clinical pharmacology · 2025Review
- Sequence Diversity and Encoded Enzymatic Differences of Monocistronic L1 ORF2 mRNA Variants in the Aged Normal and Alzheimer's Disease Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- SLFN11 Restricts LINE-1 Mobility.Cells · 2025Article
- From antiviral to anticancer: Exploring efavirenz's potential against breast cancer.Indian journal of pharmacology · 2024Article
- Efavirenz: New Hope in Cancer Therapy.Cureus · 2024Review
- Antiretroviral Drugs Impact Autophagy: Opportunities for Drug Repurposing.Frontiers in bioscience (Landmark edition) · 2024Review
- Prospects for breast cancer immunotherapy using microRNAs and transposable elements as objects.Exploration of targeted anti-tumor therapy · 2024Review
- ZNF689 deficiency promotes intratumor heterogeneity and immunotherapy resistance in triple-negative breast cancer.Cell research · 2024Article
- Review
- Advances in transposable elements: from mechanisms to applications in mammalian genomics.Frontiers in genetics · 2023Review
- An EpigeneticInternational journal of molecular sciences · 2022Review
- Article
- Article
- Article
- Combination of Antiretroviral Drugs Zidovudine and Efavirenz Impairs Tumor Growths in a Mouse Model of Cancer.Viruses · 2021Article
- TP53 drives abscopal effect by secretion of senescence-associated molecular signals in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Efavirenz as a potential drug for the treatment of triple-negative breast cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- High levels of LINE-1 transposable elements expressed in Kaposi's sarcoma-associated herpesvirus-related primary effusion lymphoma.Oncogene · 2021Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Long Interspersed Elements (L1 elements) are biologically active retrotransposons that are capable of autonomous replication using their own reverse transcriptase (RT) enzyme. Expression of the normally repressed RT has been implicated in cancer cell growth. However, at present, little is known about the expression of L1-encoded RT activity or the molecular changes that are associated with RT activity in the development of breast cancer. Here, we report that RT activity is widespread in breast cancer cells. The expression of RT protein decreased markedly in breast cancer cells after treatment with the antiretroviral drug, efavirenz. While the majority of cells showed a significant reduction in proliferation, inhibition of RT was also accompanied by cell-specific differences in morphology. MCF7 cells displayed elongated microtubule extensions that adhered tightly to their substrate, while a large fraction of the T47D cells that we studied formed long filopodia projections. These morphological changes were reversible upon cessation of RT inhibition, confirming their dependence on RT activity. We also carried out gene expression profiling with microarrays and determined the genes that were differentially expressed during the process of cellular differentiation. Genes involved in proliferation, cell migration, and invasive activity were repressed in RT-inhibited cells. Concomitantly, genes involved in cell projection, formation of vacuolar membranes, and cell-to-cell junctions were significantly upregulated in RT-inhibited cells. qRT-PCR examination of the mRNA expression of these genes in additional cell lines yielded close correlation between their differential expression and the degree of cellular differentiation. Our study demonstrates that the inhibition of L1-encoded RT can reduce the rate of proliferation and promote differentiation of breast cancer cells. Together, these results provide a direct functional link between the expression of L1 retrotransposons and the development of breast cancer.
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