alpha-synuclein and Breast-Neoplasms

The aim of this study was to assess whether cancer occurs with increased frequency in multiple system atrophy (MSA). The pathological hallmark of MSA is glial cytoplasmic inclusions containing aggregated α-synuclein, and the related protein γ-synuclein correlates with invasive cancer. We investigated whether these two disorders are associated clinically.. Medical records of 320 patients with pathologically confirmed MSA seen between 1998 and 2022 were reviewed. After excluding those with insufficient medical histories, the remaining 269 and an equal number of controls matched for age and sex were queried for personal and family histories of cancer recorded on standardized questionnaires and in clinical histories. Additionally, age-adjusted rates of breast cancer were compared with US population incidence data.. Of 269 cases in each group, 37 with MSA versus 45 of controls had a personal history of cancer. Reported cases of cancer in parents were 97 versus 104 and in siblings 31 versus 44 for MSA and controls, respectively. Of 134 female cases in each group, 14 MSA versus 10 controls had a personal history of breast cancer. The age-adjusted rate of breast cancer in MSA was 0.83%, as compared with 0.67% in controls and 2.0% in the US population. All comparisons were nonsignificant.. The evidence from this retrospective cohort found no significant clinical association of MSA with breast cancer or other cancers. These results do not exclude the possibility that knowledge about synuclein pathology at the molecular level in cancer may lead to future discoveries and potential therapeutic targets for MSA.

Topics: alpha-Synuclein; Brain; Breast Neoplasms; Female; Humans; Multiple System Atrophy; Retrospective Studies

Cancer is a huge problem of disease globally. Today, the percentage of people die from cancer is more than a combination of various diseases. In females, most common types of malignancies that occur are breast and cervical. The present focus has been shifted on medicinal plants as a form of therapy and there is a constant need to identify new therapeutic agents. Choerospondias axillaris (C. axillaris), an underutilized fruit, has been used in the remedy of various diseases. In the present communication, we evaluated the molecular mechanism of C. axillaris methanol extract in regulating cell death in human breast cancer cells (MDA-MB-231).. Methanol extract of C. axillaris was prepared and compounds were screened by Gas chromatography-mass spectrometry. The effect of fruit extract was determined on MDA-MB-231 cells by MTT ((3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay and to analyse the molecular mechanism of human breast cancer cells after treating with fruit extract, protein profiling study was performed by two-dimensional gel electrophoresis.. A total 9 differentially expressed proteins were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS/MS) analysis. Among 9 identified proteins, synphilin-1 protein was found to be significantly downregulated, validated by western blot and RT-qPCR analysis. Possible interacting partners of synphilin-1 (SNCAIP) were analyzed for their possible role in cancer by the in-silico method.. Our data implicate that the presence of bioactive compound(s) in C. axillaris fruits might play an important role in inhibiting the proliferation of breast carcinoma cells and Synphilin-1 protein may play a role of apoptotic function.

Topics: alpha-Synuclein; Anacardiaceae; Breast Neoplasms; Carrier Proteins; Cell Line, Tumor; Female; Fruit; Humans; Methanol; Nerve Tissue Proteins; Plant Extracts; Tandem Mass Spectrometry

The products of genes mutated or differentially expressed in cancer tend to occupy central positions within the network of protein-protein interactions, or the interactome network. Integration of different types of gene and protein relationships has considerably increased the understanding of the mechanisms of carcinogenesis, while also enhancing the applicability of expression signatures. In this scenario, however, it remains unknown how cancer develops, progresses and responds to therapies in a potentially controlled manner at the systems level. Here, by applying the concepts of load transfer and cascading failures in power grids, we examine the impact and transmission of cancer-related gene expression changes in the interactome network. Relative to random perturbations, this study reveals topological robustness associated with all cancer conditions. In addition, experimental perturbation of a central cancer node, which consists of over-expression of the α-synuclein (SNCA) protein in MCF7 breast cancer cells, also reveals robustness. Conversely, a search for proteins with an opposite topological impact identifies the autophagy pathway. Mechanistically, the existence of smaller shortest paths among cancer-related proteins appears to be a topological feature that partially contributes to the restricted perturbation of the network. Together, the results of this study suggest that cancer develops, progresses and responds to therapies following controlled, restricted perturbation of the interactome network.

Topics: alpha-Synuclein; Autophagy; Breast Neoplasms; Cell Line, Tumor; Computational Biology; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Models, Biological; Neoplasm Proteins; Protein Interaction Maps

Aberrantly expressed human gamma synuclein (SNCG) interacts with BubR1 and heat shock protein 70 (Hsp70) in late stages of breast and ovarian cancer. This interaction is essential for progression, development and survival of cancer cells. A short, synthetically designed ankyrin-repeat-containing peptide (ANK peptide) was proven to inhibit the activity of SNCG. However, the potential binding site residues of SNCG responsible for its oncogenic function have not been reported so far. The objectives of this study were to generate a three-dimensional model of SNCG and to identify the key residues involved in interaction with BubR1, ANK peptide and Hsp70. Our study is the first attempt to report the specific binding of SNCG with the TPR motif of BubR1 and the 18kDa region of Hsp70. Our findings provide novel insights into the mechanism of interaction of SNCG, and can act as a basis for the ongoing drug design and discovery process aimed at treating breast and ovarian cancer.

Topics: alpha-Synuclein; Amino Acid Sequence; Ankyrins; Breast Neoplasms; Female; gamma-Synuclein; HSP70 Heat-Shock Proteins; Humans; Models, Molecular; Mutation; Neoplasm Proteins; Protein Conformation; Protein Serine-Threonine Kinases; Sequence Alignment

The synucleins (alpha, beta, and gamma) are a family of small cytoplasmic proteins that are expressed predominantly in neurons. alpha synuclein has attracted considerable attention due to its involvement in neurodegenerative diseases. Abnormal expression of gamma synuclein has recently been reported in some breast tumors. In this study, the authors examined a panel of breast and ovarian carcinomas for expression of alpha, beta, and gamma synucleins.. Normal breast and ovary tissue samples, tissue from ovaries of women at high risk of ovarian carcinoma, and tissue from breast and ovarian carcinomas were screened by immunohistochemistry and Western blot analysis for synuclein expression.. Synucleins were not detectable by Western blot analysis in normal breast tissue. Eighty-two percent (14 of 17) of Stage III/IV breast ductal carcinomas expressed beta synuclein, gamma synuclein, or both simultaneously. Expression of alpha synuclein was not detected in breast carcinomas by Western blot analysis. Synuclein (alpha, beta, and gamma) expression was not detectable by immunohistochemistry in normal ovarian epithelium. Eighty-seven percent (39 of 45) of ovarian carcinomas were found to express at least 1 type of synuclein, and 42% (19 of 45) expressed all 3 synucleins (alpha, beta, and gamma) simultaneously. Highly punctate gamma synuclein expression was also observed in 20% of preneoplastic lesions of the ovary, including epithelial inclusion cysts, hyperplastic epithelium, and papillary structures, suggesting that gamma synuclein up-regulation may occur early in the development of some ovarian tumors.. alpha, beta, and gamma synuclein are expressed in a high percentage of ovarian and breast carcinomas, and abnormal gamma synuclein expression may occur early in the development of ovarian carcinoma.

Topics: Adenocarcinoma; alpha-Synuclein; beta-Synuclein; Blotting, Western; Breast; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Cystadenocarcinoma, Papillary; Epithelial Cells; Female; gamma-Synuclein; Gene Expression Regulation, Neoplastic; Humans; Hyperplasia; Immunohistochemistry; Nerve Tissue Proteins; Ovarian Cysts; Ovarian Neoplasms; Ovary; Phosphoproteins; Polymerase Chain Reaction; Precancerous Conditions; Synucleins; Tumor Cells, Cultured

We have identified and characterized a new member of the human synuclein gene family, gamma-synuclein (SNCG). This gene is composed of five exons, which encode a 127 amino acid protein that is highly homologous to alpha-synuclein, which is mutated in some Parkinson's disease families, and to beta-synuclein. The gamma-synuclein gene is localized to chromosome 10q23 and is principally expressed in the brain, particularly in the substantia nigra. We have determined its genomic sequence, and established conditions for sequence analysis of each of the exons. The gamma-synuclein gene, also known as BCSG1, was recently found to be overexpressed in advanced infiltrating carcinoma of the breast. Our survey of the EST database indicated that it might also be overexpressed in an ovarian tumor.

Topics: Adult; alpha-Synuclein; Amino Acid Sequence; Base Sequence; beta-Synuclein; Brain; Breast Neoplasms; Carcinoma, Ductal, Breast; Chromosome Mapping; Chromosomes, Human, Pair 10; Databases, Factual; Exons; Female; gamma-Synuclein; Humans; Molecular Sequence Data; Nerve Tissue Proteins; Neurons; Ovarian Neoplasms; Polymerase Chain Reaction; Sequence Alignment; Sequence Homology, Amino Acid; Substantia Nigra; Synucleins