Stiffness of the microenvironment upregulates ERBB2 expression in 3D cultures of MCF10A within the range of mammographic density.

TitleStiffness of the microenvironment upregulates ERBB2 expression in 3D cultures of MCF10A within the range of mammographic density.
Publication TypeJournal Article
Year of Publication2016
AuthorsCheng Q, Bilgin CCagatay, Fonteney G, Chang H, Henderson M, Han J, Parvin B
JournalSci Rep
Volume6
Pagination28987
Date Published2016
ISSN2045-2322
Abstract

The effects of the stiffness of the microenvironment on the molecular response of 3D colony organization, at the maximum level of mammographic density (MD), are investigated. Phenotypic profiling reveals that 3D colony formation is heterogeneous and increased stiffness of the microenvironment, within the range of the MD, correlates with the increased frequency of aberrant 3D colony formation. Further integrative analysis of the genome-wide transcriptome and phenotypic profiling hypothesizes overexpression of ERBB2 in the premalignant MCF10A cell lines at a stiffness value that corresponds to the collagen component at high mammographic density. Subsequently, ERBB2 overexpression has been validated in the same cell line. Similar experiments with a more genetically stable cell line of 184A1 also revealed an increased frequency of aberrant colony formation with the increased stiffness; however, 184A1 did not demonstrate overexpression of ERBB2 at the same stiffness value of the high MD. These results suggest that stiffness exacerbates premalignant cell line of MCF10A.

DOI10.1038/srep28987
Alternate JournalSci Rep
PubMed ID27383056
PubMed Central IDPMC4935956
Grant ListR01 CA140663 / CA / NCI NIH HHS / United States
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