TY - JOUR
T1 - Defining central themes in breast cancer biology by differential proteomics
T2 - Conserved regulation of cell spreading and focal adhesion kinase
AU - Bateman, Nicholas W.
AU - Sun, Mai
AU - Hood, Brian L.
AU - Flint, Melanie S.
AU - Conrads, Thomas P.
PY - 2010/10/1
Y1 - 2010/10/1
N2 - Breast cancer is a highly heterogeneous disease, an observation that underscores the importance of elucidating conserved molecular characteristics, such as gene and protein expression, across breast cancer cell types toward providing a greater understanding of context-specific features central to this disease. Motivated by the goal of defining central biological themes across breast cancer cell subtypes, we conducted a global proteomic analysis of three breast cancer cell lines, MCF7, SK-BR-3, and MDA-MB-231, and compared these to a model of nontransformed mammary cells (MCF10A). Our results demonstrate modulation of proteins localized to the extracellular matrix, plasma membrane, and nucleus, along with coordinate decreases in proteins that regulate "cell spreading," a cellular event previously shown to be dysregulated in transformed cells. Protein interaction network analysis revealed the clustering of focal adhesion kinase (FAK), a fundamental regulator of cell spreading, with several proteins identified as mutually, differentially abundant across breast cancer cell lines that impact expression and activity of FAK, such as neprilysin and keratin 19. These analyses provide insights into conservation of protein expression across breast cancer cell subtypes, a subset of which warrants further investigation for their roles in the regulation of cell spreading and FAK in breast cancer.
AB - Breast cancer is a highly heterogeneous disease, an observation that underscores the importance of elucidating conserved molecular characteristics, such as gene and protein expression, across breast cancer cell types toward providing a greater understanding of context-specific features central to this disease. Motivated by the goal of defining central biological themes across breast cancer cell subtypes, we conducted a global proteomic analysis of three breast cancer cell lines, MCF7, SK-BR-3, and MDA-MB-231, and compared these to a model of nontransformed mammary cells (MCF10A). Our results demonstrate modulation of proteins localized to the extracellular matrix, plasma membrane, and nucleus, along with coordinate decreases in proteins that regulate "cell spreading," a cellular event previously shown to be dysregulated in transformed cells. Protein interaction network analysis revealed the clustering of focal adhesion kinase (FAK), a fundamental regulator of cell spreading, with several proteins identified as mutually, differentially abundant across breast cancer cell lines that impact expression and activity of FAK, such as neprilysin and keratin 19. These analyses provide insights into conservation of protein expression across breast cancer cell subtypes, a subset of which warrants further investigation for their roles in the regulation of cell spreading and FAK in breast cancer.
KW - breast cancer
KW - cell spreading
KW - focal adhesion kinase
KW - mass spectrometry
KW - proteomics
UR - http://www.scopus.com/inward/record.url?scp=77957329708&partnerID=8YFLogxK
U2 - 10.1021/pr100580e
DO - 10.1021/pr100580e
M3 - Article
C2 - 20681588
AN - SCOPUS:77957329708
SN - 1535-3893
VL - 9
SP - 5311
EP - 5324
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 10
ER -