ArticleMolecular cancer research : MCR2010
Context-dependent bidirectional regulation of the MutS homolog 2 by transforming growth factor β contributes to chemoresistance in breast cancer cells.
Article in Molecular cancer research : MCR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 83 citations in OpenAlex.
- The Clinical Significance of MicroRNAs in Colorectal Cancer Signaling Pathways: A Review.Global medical genetics · 2023Review
- The Effect of Tobacco SmokeCurrent oncology (Toronto, Ont.) · 2022Article
- MSH2-deficient prostate tumours have a distinct immune response and clinical outcome compared to MSH2-deficient colorectal or endometrial cancer.Prostate cancer and prostatic diseases · 2021Article
- Mismatch repair-deficient hormone receptor-positive breast cancers: Biology and pathological characterization.Cancer cell international · 2021Review
- Article
- Comparative microRNA Transcriptomes in Domestic Goats Reveal Acclimatization to High Altitude.Frontiers in genetics · 2020Article
- Cisplatin-resistant triple-negative breast cancer subtypes: multiple mechanisms of resistance.BMC cancer · 2019Article
- TGF-β signaling proteins and CYP24A1 may serve as surrogate markers for progesterone calcitriol treatment in ovarian and endometrial cancers of different histological types.Translational cancer research · 2019Article
- Cytokines, breast cancer stem cells (BCSCs) and chemoresistance.Clinical and translational medicine · 2018Review
- The Long (lncRNA) and Short (miRNA) of It: TGFβ-Mediated Control of RNA-Binding Proteins and Noncoding RNAs.Molecular cancer research : MCR · 2018Review
- miR-21 is involved in transforming growth factor β1-induced chemoresistance and invasion by targeting PTEN in breast cancer.Oncology letters · 2017Article
- Expression of ERCC1, RRM1, TUBB3 in correlation with apoptosis repressor ARC, DNA mismatch repair proteins and p53 in liver metastasis of colorectal cancer.International journal of molecular medicine · 2017Article
- TGFbeta and miRNA regulation in familial and sporadic breast cancer.Oncotarget · 2017Article
- Transforming growth factor-β1 contributes to oxaliplatin resistance in colorectal cancer via epithelial to mesenchymal transition.Oncology letters · 2017Article
- HER2 in Breast Cancer Stemness: A Negative Feedback Loop towards Trastuzumab Resistance.Cancers · 2017Review
- Interactions between anticancer active platinum complexes and non-coding RNAs/microRNAs.Non-coding RNA research · 2017Review
- Crosstalk between TGF-β signaling and miRNAs in breast cancer metastasis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- MicroRNA: a connecting road between apoptosis and cholesterol metabolism.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- TGF-β induces miR-30d down-regulation and podocyte injury through Smad2/3 and HDAC3-associated transcriptional repression.Journal of molecular medicine (Berlin, Germany) · 2016Article
- MicroRNAs, TGF-β signaling, and the inflammatory microenvironment in cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The TGF-β, a tumor suppressive cytokine in normal cells, is abused in cancer to promote the malignancy. In this study, we reported that TGF-β downregulated the mutS homolog 2 (MSH2), a central component of the DNA mismatch repair (MMR) system, in HER2-transformed MCF10A mammary epithelial cells and in breast cancer (BC) cells. This was mediated by a TGF-β-induced micro RNA (miRNA), miR-21, which targeted the 3' untranslated region of MSH2 mRNA and downregulated its expression. A negative correlation between the expression of TGF-β1 and MSH2 was also detected in primary breast tumors. In contrast, TGF-β upregulated MSH2 in nontransformed cells through Smad-mediated, p53-dependent promoter activation, which was absent in BC cells with impaired p53 function. Although this upregulating mechanism also existed in MCF10A/HER2 and p53-proficient BC cells, both basal and TGF-β-induced MSH2 promoter activities were significantly lower than those in MCF10A. Moreover, the basal and TGF-β-induced miR-21 levels were markedly higher in transformed cells, suggesting that the preset levels of miR-21 and MSH2 promoter activity, which is affected by the p53 status, determine the outputs of the bidirectional regulation of MSH2 by TGF-β in a certain cellular context. We further found that by downregulating MSH2, TGF-β contributed to resistance to DNA-damaging chemotherapy agents in cancer cells. Our results indicated a regulatory antagonism between promoter activation and miRNA-mediated posttranscriptional inhibition underlying a dual effect of TGF-β on the DNA repair machinery, which may influence the genomic stability in a context-dependent manner and contribute to chemoresistance in cancer.
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