Open AccessStiffness of the microenvironment upregulates ERBB2 expression in 3D cultures of MCF10A within the range of mammographic density
Author(s) -
Qingsu Cheng,
Cemal Cagatay Bilgin,
Gerald Fontenay,
Hang Chang,
M. Henderson,
Ju Han,
Bahram Parvin
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep28987
Subject(s) - phenotype , transcriptome , stiffness , cell culture , gene expression profiling , biology , microbiology and biotechnology , tumor microenvironment , cell , cancer research , mammographic density , gene expression , gene , genetics , materials science , tumor cells , composite material , cancer , breast cancer , mammography
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.