AhR ligands reactivate LINE-1 retrotransposon in triple-negative breast cancer cells MDA-MB-231 and non-tumorigenic mammary epithelial cells NMuMG

Miret, Noelia; Zappia, Carlos Daniel; Altamirano, Gabriela A.; Pontillo, Carolina; Zárate, Lorena Vanesa; Gómez, Ayelén L.; Lasagna, Marianela; Cocca, Claudia; Kass, Laura; Monczor, Federico; Randi, Andrea

doi:10.1016/j.bcp.2020.113904

Cited by 11 publications

(7 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AhR activation by BaP has also been shown to influence the EMT through the regulation of a long noncoding RNA in non-small cell lung cancer (NSCLC) [46]. Conversely, AhR can reactivate the LINE-1 retro-transposon, silenced by DNA methylation, in breast cancer via the regulation of TGF- signaling, promoting tumorigenesis and disease progression [47].…”

Section: Ahr As An Oncogenementioning

confidence: 99%

AhR and Cancer: from Gene Profiling to Targeted Therapy

Paris

Tardif

Galibert

et al. 2020

Preprint

View full text Add to dashboard Cite

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that has been shown to be an essential regulator of a broad spectrum of biological activities required for maintaining the body's vital functions. AhR also plays a critical role in tumorigenesis. Its role in cancer is complex, encompassing both pro- and anti-tumorigenic activities. Its level of expression and activity are specific to each tumor and patient, increasing the difficulty of understanding the activating or inhibiting roles of AhR ligands. We explored the role of AhR in tumor cell lines and patients using genomic data sets and discuss the extent to which AhR can be considered as a therapeutic target.

show abstract

Section: Ahr As An Oncogenementioning

confidence: 99%

AhR and Cancer: from Gene Profiling to Targeted Therapy

Paris

Tardif

Galibert

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…For example, strong ligands of the aryl hydrocarbon receptor (AhR) such as such as 6-formylindolo [3,2-b]carbazole, 3-methylcholantrene and benzo[a]pyrene are known to induce hypomethylation of LINE-1 and then increase LINE-1 mRNA expression through the mitogen-activated protein kinase (MAPK) in breast cancer cell line and through the transforming growth factor-β1 (TGF-β1)/Smad pathway in HepG2 hepatocarcinoma cell line [ 165 ]. Exposure to weak AhR ligands such as hexachlorobenzene and chlorpyrifos also reduce LINE-1 methylation levels and induce LINE-1 reactivation, i.e., increased mRNA expression, in both MDA-MB-231 breast cancer cells and non-tumoral breast epithelial cells (i.e., NMuMG cell line) [ 165 ]. However, the basal expression of LINE-1 was significantly higher in the MDA-MB-231 cell lines compared to NMuMG non-tumoral cells [ 165 ].…”

Section: Role Of Stress and Environmental Pollution In Te Mobility An...mentioning

confidence: 99%

“…Exposure to weak AhR ligands such as hexachlorobenzene and chlorpyrifos also reduce LINE-1 methylation levels and induce LINE-1 reactivation, i.e., increased mRNA expression, in both MDA-MB-231 breast cancer cells and non-tumoral breast epithelial cells (i.e., NMuMG cell line) [ 165 ]. However, the basal expression of LINE-1 was significantly higher in the MDA-MB-231 cell lines compared to NMuMG non-tumoral cells [ 165 ]. In addition, the decrease of H3K9me3 level in chlordecone-exposed samples was associated with a decreased methylation in LINE-1 promoters, increased presence of H3K4me3, and then increased expression of LINE-1 ORF-1 and -2 [ 164 ].…”

Section: Role Of Stress and Environmental Pollution In Te Mobility An...mentioning

confidence: 99%

Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants

Chénais

2022

IJMS

View full text Add to dashboard Cite

Transposable elements (TEs) are recognized as major players in genome plasticity and evolution. The high abundance of TEs in the human genome, especially the Alu and Long Interspersed Nuclear Element-1 (LINE-1) repeats, makes them responsible for the molecular origin of several diseases. This involves several molecular mechanisms that are presented in this review: insertional mutation, DNA recombination and chromosomal rearrangements, modification of gene expression, as well as alteration of epigenetic regulations. This literature review also presents some of the more recent and/or more classical examples of human diseases in which TEs are involved. Whether through insertion of LINE-1 or Alu elements that cause chromosomal rearrangements, or through epigenetic modifications, TEs are widely implicated in the origin of human cancers. Many other human diseases can have a molecular origin in TE-mediated chromosomal recombination or alteration of gene structure and/or expression. These diseases are very diverse and include hemoglobinopathies, metabolic and neurological diseases, and common diseases. Moreover, TEs can also have an impact on aging. Finally, the exposure of individuals to stresses and environmental contaminants seems to have a non-negligible impact on the epigenetic derepression and mobility of TEs, which can lead to the development of diseases. Thus, improving our knowledge of TEs may lead to new potential diagnostic markers of diseases.

show abstract

“…Indeed, the altered expression patterns of LINE-1-coded ORF1 and ORF2 proteins, with differences in overall patient survival, have been reported in invasive breast cancers [ 42 ]. In specific cases, pesticide exposure induces LINE-1 reactivation, suggesting the role of LINE transcription in pesticide-induced breast cancer progression [ 43 ], and MET-LINE-1 chimeric transcripts identify a subgroup of aggressive triple-negative breast cancers [ 44 ]. Overall, it has been suggested that LINE-1 may contribute to the origin or progression of breast cancers [ 45 ].…”

Section: Introductionmentioning

confidence: 99%

Repetitive Sequence Transcription in Breast Cancer

Arancio

Coronnello

2022

Cells

View full text Add to dashboard Cite

Repetitive sequences represent about half of the human genome. They are actively transcribed and play a role during development and in epigenetic regulation. The altered activity of repetitive sequences can lead to genomic instability and they can contribute to the establishment or the progression of degenerative diseases and cancer transformation. In this work, we analyzed the expression profiles of DNA repetitive sequences in the breast cancer specimens of the HMUCC cohort. Satellite expression is generally upregulated in breast cancers, with specific families upregulated per histotype: in HER2-enriched cancers, they are the human satellite II (HSATII), in luminal A and B, they are part of the ALR family and in triple-negative, they are part of SAR and GSAT families, together with a perturbation in the transcription from endogenous retroviruses and their LTR sequences. We report that the background expression of repetitive sequences in healthy tissues of cancer patients differs from the tissues of non-cancerous controls. To conclude, peculiar patterns of expression of repetitive sequences are reported in each specimen, especially in the case of transcripts arising from satellite repeats.

show abstract

AhR ligands reactivate LINE-1 retrotransposon in triple-negative breast cancer cells MDA-MB-231 and non-tumorigenic mammary epithelial cells NMuMG

Cited by 11 publications

References 76 publications

AhR and Cancer: from Gene Profiling to Targeted Therapy

AhR and Cancer: from Gene Profiling to Targeted Therapy

Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants

Repetitive Sequence Transcription in Breast Cancer

Contact Info

Product

Resources

About