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frameshift mutation promotes tumor growth in human luminal breast cancer cells and induces transcriptional changes seen in primary mutant breast cancers. | LitMetric

AI Article Synopsis

Article Abstract

The transcription factor is one of the most frequently mutated genes in breast cancer. Heterozygous mutations, mostly frameshifts, are seen in 15% of estrogen receptor positive breast cancers, the subtype in which these mutations are almost exclusively found. Mouse studies have shown that Gata3 is critical for breast development and that gene dosage affects breast tumor progression. Human patient data have shown that high Gata3 expression, a feature of luminal subtype breast cancers, is associated with a better prognosis. Although the frequency of mutation suggests an important role in breast cancer development or progression, there is little understanding of how mutations in affect its function in luminal breast epithelial cells and what gene expression changes result as a consequence of the mutations. Here, using gene editing, we have created two sets of isogenic human luminal breast cancer cell lines with and without a hotspot truncating mutation. mutation enhanced tumor growth but did not affect sensitivity to clinically used hormonal therapies or chemotherapeutic agents. We identified genes with upregulated and downregulated expression in mutant cells, a subset of which was concordantly differentially expressed in mutant primary luminal breast cancers. Addback of mutant recapitulated mutation-specific gene expression changes and enhanced soft agar colony formation, suggesting a gain of function for the mutant protein.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732738PMC
http://dx.doi.org/10.18632/oncotarget.21910DOI Listing

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