title: Stiffness of the microenvironment upregulates ERBB2 expression in 3D cultures of MCF10A within the range of mammographic density.
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.
authors.affiliation: 1664 N Virginia Street, Department of Electrical and Biomedical Engineering, University of Nevada, Reno, Reno NV, 89503, USA.|Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS-977, Life Science Division, Berkeley CA, 94720, USA.
authors.forename: Qingsu
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS-977, Life Science Division, Berkeley CA, 94720, USA.
authors.forename: Cemal Cagatay
authors.initials: CC
authors.lastname: Bilgin
authors.affiliation: Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS-977, Life Science Division, Berkeley CA, 94720, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Fontenay
authors.affiliation: 1664 N Virginia Street, Department of Electrical and Biomedical Engineering, University of Nevada, Reno, Reno NV, 89503, USA.|Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS-977, Life Science Division, Berkeley CA, 94720, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Chang
authors.affiliation: 1664 N Virginia Street, Department of Electrical and Biomedical Engineering, University of Nevada, Reno, Reno NV, 89503, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Henderson
authors.affiliation: 1664 N Virginia Street, Department of Electrical and Biomedical Engineering, University of Nevada, Reno, Reno NV, 89503, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Han
authors.affiliation: 1664 N Virginia Street, Department of Electrical and Biomedical Engineering, University of Nevada, Reno, Reno NV, 89503, USA.|Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS-977, Life Science Division, Berkeley CA, 94720, USA.
authors.forename: Bahram
authors.initials: B
authors.lastname: Parvin
mesh_terms: D001696:Biomechanical Phenomena; D000071060:Breast Density; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D003094:Collagen; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018625:Microscopy, Atomic Force; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D059016:Tumor Microenvironment; D015854:Up-Regulation
chemical_list: D003094:Collagen; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human