Differential Protein Expression Profiles In Estrogen Receptor–Positive And –Negative Breast Cancer Tissues Using Label-Free Quantitative Proteomics  

Oleh:

Rezaul, Karim ; Thumar, Jay Kumar ; Lundgren, Deborah H. ; Eng, Jimmy K. ; Claffey, Kevin P. ; Wilson, Lori ; Han, David K.

Jenis: Article from Article
Dalam koleksi: Genes and Cancer vol. 1 no. 3 (May 2010), page 251-271.
Topik: LC-MS/MS; Breast Cancer; Estrogen Receptor; Laser Capture Microdissection; Fascin
Fulltext: 251-71.pdf (1.16MB)

Isi artikel

Identification of the proteins that are associated with estrogen receptor (ER) status is a first step towards better understanding of the hormone-dependent nature of breast carcinogenesis. Although a number of gene expression analyses have been conducted, protein complement has not been systematically investigated to date. Because proteins are primary targets of therapeutic drugs, in this study, we have attempted to identify proteomic signatures that demarcate ER-positive and -negative breast cancers. Using highly enriched breast tumor cells, replicate analyses from 3 ERa+ and 3 ERa- human breast tumors resulted in the identification of 2,995 unique proteins with =2 peptides. Among these, a number of receptor tyrosine kinases and intracellular kinases that are abundantly expressed in ERa+ and ERa- breast cancer tissues were identified. Further, label-free quantitative proteome analysis revealed that 236 proteins were differentially expressed in ERa+ and ERa- breast tumors. Among these, 141 proteins were selectively up-regulated in ERa+, and 95 proteins were selectively up-regulated in ERa- breast tumors. Comparison of differentially expressed proteins with a breast cancer database revealed 98 among these have been previously reported to be involved in breast cancer. By Gene Ontology molecular function, dehydrogenase, reductase, cytoskeletal proteins, extracellular matrix, hydrolase, and lyase categories were significantly enriched in ERa+, whereas selected calcium-binding protein, membrane traffic protein, and cytoskeletal protein were enriched in ERa- breast tumors. Biological process and pathway analysis revealed that up-regulated proteins of ERa+ were overrepresented by proteins involved in amino acid metabolism, proteasome, and fatty acid metabolism, while up-regulated proteins of ERa- were overrepresented by proteins involved in glycolysis pathway. The presence and relative abundance of 4 selected differentially abundant proteins (liprin-a1, fascin, DAP5, and ß-arrestin-1) were quantified and validated by immunohistochemistry. In conclusion, unlike in vitro cell culture models, the in vivo signaling proteins and pathways that we have identified directly from human breast cancer tissues may serve as relevant therapeutic targets for the pharmacological intervention of breast cancer.

Opini Anda

Klik untuk menuliskan opini Anda tentang koleksi ini!

Kembali