Dystroglycan Expression Is Frequently Reduced in Human Breast and Colon Cancers and Is Associated with Tumor Progression

Sgambato, Alessandro; Migaldi, Mario; Montanari, Micaela; Camerini, Andrea; Brancaccio, Andrea; Rossi, Giulio; Cangiano, Rodolfo; Losasso, Carmen; Capelli, Giovanni; Trentini, G. P.; Cittadini, Achille

doi:10.1016/s0002-9440(10)63881-3

Cited by 106 publications

(181 citation statements)

References 34 publications

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“…Exponentially growing cultures of each cell lines were collected by cell scraping and cell pellets were added to 3-5 volumes of sonication buffer containing proteases and phosphatase inhibitors (20 mM Tris-HCl pH 7.4, 2 mM EGTA, 6 mM β-mercaptoethanol, 1% NP40, 0.1% SDS, 50 mM NaF, 15 µg/ml benzamidine, 10 µg/ml aprotinin, 10 µg/ml leupeptin and 1 mM phenylmethylsulfonyl fluoride) and sonicated at 4˚C, as previously described. 11,19,21 Homogenates were incubated in ice for 30 minutes and then centrifuged at 14000 rpm for 15 min at 4˚C. The supernatants were assayed for protein content and 50 µg of protein from each sample were separated by SDS-PAGE and transferred to immobilon-P membranes (Millipore, Bedford, MA) at 100 volts for 1 hour at 4˚C.…”

Section: Methodsmentioning

confidence: 99%

“…The monoclonal antibodies to α-DG (clone VIA4-1) and to β-DG (clone 43DAG/8D5) were obtained from Upstate Biotechnology (Lake Placid, NY) and from Novocastra (Newcastle, UK), respectively and were used as previously described. 11 The polyclonal antibody to α-DG was raised in rabbits immunised with a recombinant fragment spanning the N-terminal region of mouse α-DG (30-315) 22 and was previously shown to be able to detect α-DG protein in western blot analysis. 23 Semiquantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Analysis.…”

Section: Methodsmentioning

confidence: 99%

“…3,6,9 We and others recently demonstrated that DG expression, and mainly α-DG, is reduced or lost in a variety of human cancer cell lines 7,10,11 and in primary breast, colon and prostate cancers. 11,12 It has been also observed that a reduction in the expression levels of DG is most pronounced in high-grade diseases 11,12 and has a prognostic significance in breast cancer patients. 11 Although the exact molecular mechanisms have not been identified, yet regulation of DG expression appears to occur at a post-transcriptional level both in primary tumors and cancer cell lines.…”

Section: Introductionmentioning

confidence: 97%

“…11,12 It has been also observed that a reduction in the expression levels of DG is most pronounced in high-grade diseases 11,12 and has a prognostic significance in breast cancer patients. 11 Although the exact molecular mechanisms have not been identified, yet regulation of DG expression appears to occur at a post-transcriptional level both in primary tumors and cancer cell lines. 7,10,11,13 However, the exact role of DG in the regulation of mammary epithelial cell growth and tumorigenesis remains largely unknown.…”

Section: Introductionmentioning

confidence: 98%

“…11 Although the exact molecular mechanisms have not been identified, yet regulation of DG expression appears to occur at a post-transcriptional level both in primary tumors and cancer cell lines. 7,10,11,13 However, the exact role of DG in the regulation of mammary epithelial cell growth and tumorigenesis remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Increased expression of dystroglycan inhibits the growth and tumorigenicity of human mammary epithelial cells

Sgambato¹,

Camerini²,

Faraglia³

et al. 2004

Cancer Biology & Therapy

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Dystroglycan (DG) is an adhesion molecule formed by two subunits, α (extracellular) and β (transmembrane) DG, which are codified by a single gene and form a continuous link from the extracellular matrix to the intracellular cytoskeleton. Reduction or loss of expression of DG has been observed in human cancer cell lines and primary tumors and has been suggested to promote tumor development and invasiveness.In this study, the human breast epithelial non-tumorigenic MCF10F and the breast cancer MCF7 cell lines were engineered to stably express an exogenous DG cDNA and the effects on the phenotype of both cell lines were evaluated. The MCF10F transfected cells displayed an increased expression of both DG subunits which was associated with inhibition of the anchorage-dependent growth, accumulation of cells in the G 0 /G 1 phase of the cell cycle and increased adhesion to a substratum. The MCF7 transfected cells were unable to restore α-DG despite an increased expression of the β-DG subunit. Anchoragedependent and independent growth and the in vivo tumorigenicity were reduced in these derivatives that also displayed a reduced adhesion to a substratum and were shown to release α-DG in the culture medium.These findings confirm and extend previous evidence that transformation of mammary epithelial cells is associated with loss of their ability to retain α-DG on the cell membrane. Moreover, they indicate that DG is involved in cell functions other than cell adhesion to the extracellular matrix, and that its loss of function might predispose to tumor progression by compromising regulatory controls over cell growth and proliferation.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Increased expression of dystroglycan inhibits the growth and tumorigenicity of human mammary epithelial cells

Sgambato¹,

Camerini²,

Faraglia³

et al. 2004

Cancer Biology & Therapy

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View full text Add to dashboard Cite

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In silico bioinformatic tools for determining core genes from sets of genomes

Mahadevan

Seto

2010

Drug Development Research

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Objective Patients may be defined as nonadherent if they do not take their medications as prescribed by their physicians. Determinants of nonadherence may vary between and within patient groups. This study investigated the extent to which patients with systemic lupus erythematosus (SLE) show intentional and unintentional nonadherence, and the associations of nonadherence with psychological and medical parameters. Methods The study included 106 patients who were receiving at least one immunosuppressive agent to control their SLE. Level of self‐reported adherence and a measure of both intentional and unintentional nonadherence were obtained. Questionnaires were completed to assess associations between adherence and problems with cognitive functioning, beliefs about medicines, illness perceptions, emotional health, and disease characteristics. Results The mean self‐reported adherence rate for the total patient group was 86.7%. At least occasional intentional nonadherence was reported by 46.2% of patients and 58.5% of patients were at least occasionally unintentionally nonadherent. Problems with cognitive functioning, concerns about adverse effects of medication, and younger age were the strongest predictors of (non)adherence. Patients who were emotionally affected by their SLE were more likely to report low adherence, but this was not a significant predictor after accounting for other variables. Disease characteristics showed no relationship to measures of adherence. Conclusion Although SLE patients reported high levels of adherence on average, they commonly reported intentional and unintentional nonadherence. Adherence was associated with both cognitions and emotions. Nonadherence may be reduced by targeting emotional and cognitive functioning and by fine tuning doctor–patient communication to address patients' individual concerns about their medications.

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Comparative two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE) of human milk to identify dysregulated proteins in breast cancer

et al. 2018

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Breast cancer (BC) remains a major cause of mortality, and early detection is considered important for reducing BC-associated deaths. Early detection of BC is challenging in young women, due to the limitations of mammography on the dense breast tissue of young women. We recently reported results of a pilot proteomics study, using one-dimensional polyacrylamide gel electrophoresis (1D-PAGE) and mass spectrometry (MS) to investigate differences in milk proteins from women with and without BC. Here, we applied two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and MS to compare the protein pattern in milk from the breasts of a single woman who was diagnosed with BC in one breast 24 months after donating her milk. Statistically different gel spots were picked for protein digestion followed by nanoliquid chromatography tandem MS (nanoLC-MS/MS) analysis. The upregulated proteins in BC versus control are alpha-amylase, gelsolin isoform a precursor, alpha-2-glycoprotein 1 zinc isoform CRA_b partial, apoptosis-inducing factor 2 and vitronectin. Several proteins were downregulated in the milk of the breast later diagnosed with cancer as compared to the milk from the healthy breast, including different isoforms of albumin, cholesterol esterase, different isoforms of lactoferrin, different proteins from the casein family and different isoforms of lysozyme. Results warrant further studies to determine the usefulness of these milk proteins for assessing risk and detecting occult disease. MS data is available via ProteomeXchange with identifier PXD009860.

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Dystroglycan Expression Is Frequently Reduced in Human Breast and Colon Cancers and Is Associated with Tumor Progression

Cited by 106 publications

References 34 publications

Increased expression of dystroglycan inhibits the growth and tumorigenicity of human mammary epithelial cells

Increased expression of dystroglycan inhibits the growth and tumorigenicity of human mammary epithelial cells

In silico bioinformatic tools for determining core genes from sets of genomes

Comparative two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE) of human milk to identify dysregulated proteins in breast cancer

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