Protein Modifications as Potential Biomarkers in Breast Cancer

Abstract

A variety of post-translational protein modifications (PTMs) are known to be altered as a result of cancer development. Thus, these PTMs are potentially useful biomarkers for breast cancer. Mass spectrometry, antibody microarrays and immunohistochemistry techniques have shown promise for identifying changes in PTMs. In this review, we summarize the current literature on PTMs identified in the plasma and tumor tissue of breast-cancer patients or in breast cell lines. We also discuss some of the analytical techniques currently being used to evaluate PTMs.

4-Hydroxynonenal Promotes Growth and Angiogenesis of Breast Cancer Cells through HIF-1α Stabilization

“…4-HNE was reported to increase cell growth and differentiation (Dalleau et al, 2013). Increased levels of 4-HNE was also found in human invasive breast cancer (Jin and Zangar, 2009).…”

“…4-HNE can bind to cysteine, histidine, and lysine residues of proteins via Michael addition reaction (Bennaars-Eiden et al, 2002;Macpherson et al, 2007). Thus, 4-HNE can increase oxidative post translational modification (PTM) and then alter protein function and cell signaling (Jin and Zangar, 2009;Ryan et al, 2014). 4-HNE could inhibit PTEN (Phosphatase and tensin homolog) activity in the hepatocytes (Shearn et al, 2011;Ayala et al, 2014).…”

Early Detection Of Breast Cancer using Post-Translationally Modified Biomarkers

“…Changes in proteins identified by proteomic studies are largely different from those found by genomics studies (7,8). This underscores the importance of performing biomarker screens at the protein level and suggests that many of the differences between normal and cancer samples are due to posttranslational modifications (PTMs) such as phosphorylation, glycosylation, oxidation, methylation, ubiquitinylation and acetylation (9). ELISA microarray technology is employed to evaluate assays that have potential be used as breast cancer biomarkers (10)(11)(12)(13)(14)(15) ELISA microarry for breast cancer early detection.…”

Early Detection of Breast Cancer Using Posttranslationally Modified Biomarkers

“…In general, most cell surface antigens with which antibodies react are glycoproteins or glycolipids, i.e., CA-199, CA-125, and Globo-H. 8,15,36,37 To further explore if the antigen of H6-11 is a glycoprotein or glycolipid, the epitope was characterized by deglycosylation experiments. We treated PC-3 and MCF-7 cells with different concentrations of trypsin, followed by radioactivity measurement using 125 I-labeled H6-11 and anti-Globo-H (MBr1), respectively.…”

“…Many of these glycans have been observed in malignant cancer tissues. 2,13,15,37,49 The addition of O-glycosidic GlcNAc in β linkage to Ser/Thr residues (O-GlcNAc) is a dynamic post-translational modification that occurs on numerous cytoplasmic and nuclear proteins and is distinct from complex carbohydrate synthesis in the secretory pathway. 42 Previous studies suggested that altered O-GlcNAcylation may play an important role in the pathogenesis of diabetes mellitus, 50,51 etiology of Alzheimer's disease, 50−52 and breast cancer development.…”