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Luminal epithelial cells within the mammary gland can produce basal cells upon oncogenic stress

Abstract

In the normal mammary gland, the basal epithelium is known to be bipotent and can generate either basal or luminal cells, whereas the luminal epithelium has not been demonstrated to contribute to the basal compartment in an intact and normally developed mammary gland. It is not clear whether cellular heterogeneity within a breast tumor results from transformation of bipotent basal cells or from transformation and subsequent basal conversion of the more differentiated luminal cells. Here we used a retroviral vector to express an oncogene specifically in a small number of the mammary luminal epithelial cells and tested their potential to produce basal cells during tumorigenesis. This in-vivo lineage-tracing work demonstrates that luminal cells are capable of producing basal cells on activation of either polyoma middle T antigen or ErbB2 signaling. These findings reveal the plasticity of the luminal compartment during tumorigenesis and provide an explanation for cellular heterogeneity within a cancer.

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Acknowledgements

We thank Dr Jeffrey Rosen for critical reading of this manuscript. This work was supported in part by funds from NIH CA124820 (to YL) and U54CA149196 (to YL; PI: Stephan Wong); from DOD CDMRP BC085050 (to YL), BC112704 (to YL) and BC073703 (YL); and from the Nancy Owens Memorial Foundation (to YL); as well as by the resources from the Dan L. Duncan Cancer Center (P30CA125123) and the Lester & Sue Smith Breast Center (P50CA058183 & P50-CA186784). SMH was supported by the CPRIT Training Program (RP101499) and by NIH training award T32AG000183. ANJ was supported by NIH training award T32GM088129. This project was supported by the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the NIH (P30 AI036211, P30 CA125123 and S10 RR024574) and the expert assistance of Joel M. Sederstrom.

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Correspondence to Y Li.

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Hein, S., Haricharan, S., Johnston, A. et al. Luminal epithelial cells within the mammary gland can produce basal cells upon oncogenic stress. Oncogene 35, 1461–1467 (2016). https://doi.org/10.1038/onc.2015.206

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