Identification of alpha‐actinin 4 and 67 kDa laminin receptor as stage‐specific markers in esophageal cancer via proteomic approaches

Abstract

Unlike other primary sensory neurons, the neurons in the mesencephalic trigeminal nucleus (Vmes) receive most of their synaptic input onto their somata. Detailed description of the synaptic boutons onto Vmes neurons is crucial for understanding the synaptic input onto these neurons and their role in the motor control of masticatory muscles. For this, we investigated the distribution of γ‐aminobutyric acid (GABA)‐, glycine‐, and glutamate‐immunopositive (+) boutons on Vmes neurons and their ultrastructural parameters that relate to transmitter release: Vmes neurons that innervate masseteric muscle spindles were identified by labeling with horseradish peroxidase injected into the muscle, and immunogold staining and quantitative ultrastructural analysis of synapses onto these neurons were performed in adult rats and during postnatal development. The bouton volume, mitochondrial volume, and active zone area of the boutons contacting labeled somata (axosomatic synapses) were similar to those of boutons forming axoaxonic synapses with Vmes neurons but smaller than those of boutons forming axodendritic or axosomatic synapses with most other neurons. GABA+, glycine+, and glutamate+ boutons constituted a large majority (83%) of all boutons on labeled somata. A considerable fraction of boutons (28%) was glycine+, and all glycine+ boutons were also GABA+. Bouton size remained unchanged during postnatal development. These findings suggest that the excitability of Vmes neurons is determined to a great extent by GABA, glycine, and glutamate and that the relatively lower synaptic strength of axosomatic synapses may reflect the role of the Vmes neurons in modulating orofacial motor function. J. Comp. Neurol. 520:3414–3427, 2012. © 2012 Wiley Periodicals, Inc.

Proteomics and Esophageal Cancer

“…At expression level different isoforms of TMP are regulated dissimilarly in tumors, implying that these isoforms may have different functions in cell transformation. TPM1 [23] and TPM2 [24] have shown to be subject of down-regulation while TPM4 [23] and TPM3 ( [25], and as our unpublished result indicates (in a study on cell lines)) are significantly subject of upregulation in ESCC tissues. In addition, fusion of TPM4-ALK was observed to happen in ESCC [24] which results in the up regulation of anaplastic leukemia kinase.…”

Proteomic Study of Esophageal Squamous Cell Carcinoma

“…Later, five groups reported proteomic signatures associated with ESCC using ESCC samples collected from different regions of China, including high risk areas for ESCC such as Linzhou, Xinjiang and low risk areas like Beijing and Guangdong, but only four reports displayed details of identified proteins. Interestingly, more overlap of the identified proteins came from Fu's study and ours, both of which used ESCC samples from Linzhou, one of the highest areas for ESCC adjacent to Taihang Mountain [Fu et al, 2007]. The commonly identified proteins with the same change direction included alpha enolase, TPM, tubulin, prohibitin and PRX2.…”

“…Our findings indicate that MIF may play crucial roles in malignant transformation of pathogenesis of EC and MIF could become a potential biomarker for high-risk population screening, assessment of therapeutic efficiency, prognostic evaluation, and molecular targets of developing novel therapeutic regimen as well. In addition of our proteomic results in ESCC, several other reports have looked at the clinical value of potential biomarkers, including cytokeratin 14, Annexin I, SCCA1/2, calgulanulin B and HSP 60, alpha-actinin 4 and 67 kDa laminin receptor, cathepsin D and PKM2, periplakin, calreticulin and GRP78, galectin-7, anti-CD25B antibody [Dong et al, 2010;Du et al, 2007;Fu et al, 2007;Hatakeyama et al, 2006;Liu et al, 2011;Nishimori et al, 2006;Zhu et al, 2010]. Nevertheless, further extensive studies are still necessary to determine the clinical utility of the identified proteins in tumorigenesis and progression of ESCC.…”

“…Heat shock protein 27 kDa ↓ or ↑ [Du et al, 2007;Fu et al, 2007;Liu et al, 2011; [Qi et al, 2005] www.intechopen.com…”

“…↑or ↓ Transcription regulation [Fu et al, 2007;Qi et al, 2005] Neuronal protein ↑ Neuronal growth [Qi et al, 2005] Nuclear autoantigenic sperm protein isoform 1 ↑ Hsp90 protein binding [Nishimori et al, 2006] Myosin heavy chain nonmuscle form A ↓ Actin binding or calmodulin binding [Nishimori et al, 2006] Caldesmon 1 isoform 1 ↓ [Nishimori et al, 2006] Myosin regulatory light chain 2 ↓ Ventricular/cardiac muscle isoform [Jazii et al, 2006;Zhu et al, 2010] Myosin light chain 2 ↓ Regulatory light chain of myosin [Jazii et al, 2006] [Nishimori et al, 2006] Calponin 1, basic ↓ actin binding ; calmodulin binding [Nishimori et al, 2006] DNA directed RNA polymerase B (ropB) ↑ Transcription [Jazii et al, 2006] GH16431P ↑ NA [Jazii et al, 2006] OPTN protein ↓ Protein C-terminus binding [Fu et al, 2007] 67 kDa laminin receptor ↑ Signal transduction [Fu et al, 2007 [Zhu et al, 2010] Peptidyl-prolyl cis-trans isomerase A ↑ Peptidyl-prolyl cis-trans isomerase activity [Zhu et al, 2010] Cystatin-B ↑ Cysteine-type endopeptidase inhibitor activity [Zhu et al, 2010] Serum amyloid P-component [Precursor] ↓ Protein binding [Zhu et al, 2010] Phosphatidylethanolamine-binding protein1 ↓ Serine-type endopeptidase inhibitor [Zhu et al, 2010] Carbonic anhydrase 1 ↓ Carbonate dehydratase activity [Zhu et al, 2010] Carbonic anhydrase 3 ↓ [Zhu et al, 2010] Creatine kinase M-type ↓ Creatine kinase activity [Zhu et al, 2010] [Ong & Mann, 2006]. We used SILAC medium to label immortalized cells (NE3 and NE6) with heavy stable isotope [U-13 C 6 ]-H-Lysine and [U-13 C 6 ]-H-Arginine and cancer cells (EC1, EC109, EC9706) with light stable isotope [ 12 C 6 ]-L-Lysine and [ 12 C 6 ]-LArginine, respectively.…”