PubMed:27374087 JSONTXT

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of the CD49f+/CD44+/CD24- single-cell derived stem cell population in basal-like DCIS cells.\nThe molecular mechanisms responsible for the Ductal Carcinoma in Situ (DCIS)-Invasive Ductal Carcinoma (IDC) transition have yet to be elucidated. Due to the lack of molecularly targeted therapies, basal-like DCIS has a high risk of recurrence and progression to invasive and metastatic cancers. In this study, by applying a novel single-cell clonogenic approach with the CD49f+/CD44+/CD24- surface markers, we characterized the aggressive clones that have enhanced self-renewal, migratory and invasive capacities derived from a human DCIS model cell line MCF10DCIS. The aggressive clones had elevated ALDH1 activity, lower global DNA methylation and increased expression of stem cell related genes, especially concurrent activation of SOX2/OCT4. In addition, we showed that the aggressive clones have increased expression of lincRNA-RoR and miR-10b compared to non-aggressive clones, which enhance their self-renewal and invasive abilities. Finally, we confirmed our in vitro results in vivo, demonstrating that aggressive clones were capable of forming tumors in nude mice, whereas non-aggressive clones were not. Our data suggest that lincRNA-RoR and miR10b could be used to distinguish aggressive clones from non-aggressive clones within the heterogeneous CD49f+/CD44+/CD24- DCIS population. Our findings also provide the foundation to develop new chemoprevention agents for DCIS-IDC transition."}

{"project":"PubMed_ArguminSci","denotations":[{"id":"T1","span":{"begin":110,"end":256},"obj":"DRI_Background"},{"id":"T2","span":{"begin":257,"end":405},"obj":"DRI_Background"},{"id":"T3","span":{"begin":406,"end":676},"obj":"DRI_Background"},{"id":"T4","span":{"begin":677,"end":856},"obj":"DRI_Outcome"},{"id":"T5","span":{"begin":857,"end":1051},"obj":"DRI_Outcome"},{"id":"T6","span":{"begin":1052,"end":1225},"obj":"DRI_Outcome"},{"id":"T7","span":{"begin":1226,"end":1405},"obj":"DRI_Outcome"},{"id":"T8","span":{"begin":1406,"end":1509},"obj":"DRI_Approach"}],"text":"Characterization of the CD49f+/CD44+/CD24- single-cell derived stem cell population in basal-like DCIS cells.\nThe molecular mechanisms responsible for the Ductal Carcinoma in Situ (DCIS)-Invasive Ductal Carcinoma (IDC) transition have yet to be elucidated. Due to the lack of molecularly targeted therapies, basal-like DCIS has a high risk of recurrence and progression to invasive and metastatic cancers. In this study, by applying a novel single-cell clonogenic approach with the CD49f+/CD44+/CD24- surface markers, we characterized the aggressive clones that have enhanced self-renewal, migratory and invasive capacities derived from a human DCIS model cell line MCF10DCIS. The aggressive clones had elevated ALDH1 activity, lower global DNA methylation and increased expression of stem cell related genes, especially concurrent activation of SOX2/OCT4. In addition, we showed that the aggressive clones have increased expression of lincRNA-RoR and miR-10b compared to non-aggressive clones, which enhance their self-renewal and invasive abilities. Finally, we confirmed our in vitro results in vivo, demonstrating that aggressive clones were capable of forming tumors in nude mice, whereas non-aggressive clones were not. Our data suggest that lincRNA-RoR and miR10b could be used to distinguish aggressive clones from non-aggressive clones within the heterogeneous CD49f+/CD44+/CD24- DCIS population. Our findings also provide the foundation to develop new chemoprevention agents for DCIS-IDC transition."}