The identification and differential expression of calcium-binding proteins associated with ocular melanoma

Ginkel, Paul R. van; Gee, Ricardo L.; Walker, Teresa M.; Hu, Dan‐Ning; Heizmann, Claus W.; Polans, Arthur S.

doi:10.1016/s0167-4889(98)00133-5

Cited by 59 publications

(34 citation statements)

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“…The minimum regions defined are likely to harbour genes important to the development of UVMs . 1p 1q 2p 2q 3p 3q 4p 4q 5p 5q 6p 6q 7p 7q 8p 8q 9p 9q 10p 10q 11p 11q 12p 12q 13p 13q 14p 14q 15p 15q 16p 16q 17p 17q 18p 18q 19p 19q 20p 20q 21p 21q 22p 22q 1p 1q 2p 2q 3p 3q 4p 4q 5p 5q 6p 6q 7p 7q 8p 8q 9p 9q 10p 10q 11p 11q 12p 12q 13p 13q 14p 14q 15p 15q 16p 16q 17p 17q 18p 18q 19p 19q 20p 20q 21p 21q 22p 22q 1p 1q 2p 2q 3p 3q 4p 4q 5p 5q 6p 6q 7p 7q 8p 8q 9p 9q 10p 10q 11p 11q 12p 12q 13p 13q 14p 14q 15p 15q 16p 16q 17p 17q 18p 18q 19p 19q 20p 20q 21p 21q 22p Dunne et al, 1998;Hendrix et al, 1998;Hurks et al, 2000;Onken et al, 2004;Radosevich et al, 2004;Van Ginkel et al, 1998;Zuidervaart et al, 2003. …”

Section: Resultsunclassified

Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3

et al. 2005

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Defining regions of genomic imbalance can identify genes involved in tumour development. Conventional cytogenetics has identified several nonrandom copy number alterations (CNA) in uveal melanomas (UVM), which include monosomy 3, chromosome 6 abnormalities and gain of 8q. To gain further insight into the CNAs and define the regions involved more precisely we analysed 18 primary UVMs using 1 Mb BAC microarray comparative genomic hybridisation (CGH). Our analysis showed that the most common genomic imbalances were 8q gain (78%), 6p gain (67%) and monosomy 3 (56%). Two distinct CGH profiles could be delineated on the basis of the chromosome 3 status. The most common genetic changes in monosomy 3 tumours, in our study, were gain of 8q11.21 -q24.3, 6p25.1 -p21.2, 21q21.2 -q21.3 and 21q22.13 -q22.3 and loss of 1p36. 33 -p34.3, 1p31.1 -p21.2, 6q16.2 -q25.3 and 8p23.3 -p11.23. In contrast, disomy 3 tumours showed recurrent gains of only 6p25.3 -p22.3 and 8q23.2 -q24.3. Our approach allowed definition of the smallest overlapping regions of imbalance, which may be important in the development of UVM.

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Section: Resultsunclassified

Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3

et al. 2005

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“…CapG overexpression has been reported in several cancer types, such as breast carcinoma (Kang et al, 2010;Xu et al, 2010), ovarian adenocarcinoma (Partheen et al, 2008), oral carcinoma (Nomura et al, 2008), pancreatic cancer (Thompson et al, 2007a,b), and ocular melanoma (Van Ginkel et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Evaluation of CapG, Gelsolin, P‐gp, GSTP1, and Topo‐II Proteins in Non‐Small Cell Lung Cancer

Zhu

Hunag

Liu

et al. 2011

The Anatomical Record

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Metastasis and multidrug resistance (MDR) are the main reasons for the poor prognosis of non-small cell lung cancer (NSCLC) patients. The use of biomarkers may contribute to a more accurate prediction of tumor metastasis, a better response to chemotherapy, and better patient survival. Gelsolin-like actin-capping protein (CapG) and gelsolin have been identified as playing important roles in tumor invasion and metastasis. Permeability glycoprotein (P-gp), glutathione S-transferase pi (GSTP1), and topoisomerase-II (Topo-II) are proteins that are closely related to MDR. In this study, we assessed the prognostic significance of CapG and gelsolin (both markers of tumor motility), and of P-gp, GSTP1, and Topo-II (markers of MDR) in NSCLC patients. One hundred and twenty-one patients with pathologically confirmed, resectable NSCLC were included in the study. The expression levels of the five kinds of proteins mentioned above were determined by immunohistochemistry (IHC). The correlation between the clinical characteristics and IHC findings were analyzed. Expression of CapG, gelsolin, and P-gp was found to be associated with an increased risk of death (Hazard Ratio (HR) ¼ 2.799, 95% Confidence Interval (CI) ¼ 1.2705-6.169, P ¼ 0.011; HR ¼ 3.968, 95% CI ¼ 1.811-8.693, P ¼ 0.001; HR ¼ 3.251, 95% CI ¼ 1.456-7.260, P ¼ 0.004, respectively), whereas expression of GSTP1 and Topo-II was not. These results suggest that higher tumor motility and MDR may be important in NSCLC prognosis. Anat Rec, 295:208-214, 2012. V V C 2011 Wiley Periodicals, Inc.Key words: NSCLC; CapG; gelsolin; P-gp; prognosisLung cancer remains the leading cause of cancerrelated deaths in China, in both males and females. The most common form of lung cancer, non-small cell lung cancer (NSCLC), has a 5-year relative survival rate below 70% in patients with Stage I tumors, and below 1% in patients with Stage IV tumors (Jemal et al., 2009). Treatment of patients with NSCLC is governed by various prognostic factors such as surgical stage, histological grade, differentiation, and lymph node metastasis. Nevertheless, the clinical outcome in individual patients is often difficult to predict.The main cause of death from lung cancer is usually related to metastasis and resistance to chemotherapeutics after primary surgery. If prognosis could be determined more precisely before treatment, then patients would be more effectively treated with individualized therapy. Compared with mRNAs, which degrade quickly if samples are not prepared correctly, proteins are more stable and potentially very useful biomarkers. Furthermore, differences in protein expression may reveal information about biological properties of tumors.

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“…Staining of fixed cells was carried out as previously described (16 Equilibrium data were collected at 9000, 12 000, 16 000, and 22 000 rpm at 20 °C. Reversibility was checked at 12 000 rpm by reducing the speed after equilibrium had been reached at 22 000 rpm.…”

Section: Methodsmentioning

confidence: 99%

Ca²⁺ Binding to EF Hands 1 and 3 Is Essential for the Interaction of Apoptosis-Linked Gene-2 with Alix/AIP1 in Ocular Melanoma

et al. 2004

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Apoptosis-linked gene-2 (ALG-2) encodes a 22 kDa Ca 2+ -binding protein of the penta EF-hand family that is required for programmed cell death in response to various apoptotic agents. Here, we demonstrate that ALG-2 mRNA and protein are down-regulated in human uveal melanoma cells compared to their progenitor cells, normal melanocytes. The down regulation of ALG-2 may provide melanoma cells with a selective advantage. ALG-2 and its putative target molecule, Alix/AIP1, are localized primarily in the cytoplasm of melanocytes and melanoma cells independent of the intracellular Ca 2+ concentration or the activation of apoptosis. Cross-linking and analytical centrifugation studies support a single-species dimer conformation of ALG-2, also independent of Ca 2+ concentration. However, binding of Ca 2+ to both EF-1 and EF-3 is necessary for ALG-2 interaction with Alix/AIP1 as demonstrated using surface plasmon resonance spectroscopy. Mutations in EF-5 result in reduced target interaction without alteration in Ca 2+ affinity. The addition of N-terminal ALG-2 peptides, residues 1-22 or residues 7-17, does not alter the interaction of ALG-2 or an N-terminal deletion mutant of ALG-2 with Alix/AIP1, as might be expected from a model derived from the crystal structure of ALG-2. Fluorescence studies of ALG-2 demonstrate that an increase in surface hydrophobicity is primarily due to Ca 2+ binding to EF-3, while Ca 2+ binding to EF-1 has little effect on surface exposure of hydrophobic residues. Together, these data indicate that gross surface hydrophobicity changes are insufficient for target recognition. † This work was supported by NIH Grants EY12768 and EY13705 (A.S.P.), EY08061 (K.P.), and EY06603 and EY14239 (J.W.C.) and the Swiss National Science Foundation 31-65071.01 (J.C.), as well as grants from the Retina Research Foundation, Research to Prevent Blindness Inc. (RPB), the University of Wisconsin Comprehensive Cancer Center, and the E. K. Bishop Foundation. L.S. is a recipient of the Cremer Scholarship. A.S.P. is a Jules and Doris Stein RPB Professor. * To whom correspondence should be addressed. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptApoptosis-linked gene-2 (ALG-2) was first identified in a death-trap assay using a mouse T cell hybridoma model (1). These cells when transfected with an antisense ALG-2 expression vector were resistant to T cell receptor-mediated cell death and were partially protected from other agents that normally initiate programmed cell death such as Fas, staurosporine, actinomycin D, and C 2 -ceramide (1). More recent work suggests that ALG-2 might be involved in the apaf1-independent intrinsic apoptotic pathway activated as a result of endoplasmic reticulum (ER) stress (2).ALG-2 contains five putative EF-hand sequences and is a member of the family of PEF 1 (penta-EF-hand) proteins that includes the calpain small subunit, sorcin, and grancalcin (3). In ALG-2, EF-1 and EF-3 are considered the high-affinity Ca 2+ -binding sites, while one low-affinity site...

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The identification and differential expression of calcium-binding proteins associated with ocular melanoma

Cited by 59 publications

References 20 publications

Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3

Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3

Prognostic Evaluation of CapG, Gelsolin, P‐gp, GSTP1, and Topo‐II Proteins in Non‐Small Cell Lung Cancer

Ca²⁺ Binding to EF Hands 1 and 3 Is Essential for the Interaction of Apoptosis-Linked Gene-2 with Alix/AIP1 in Ocular Melanoma

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The identification and differential expression of calcium-binding proteins associated with ocular melanoma

Cited by 59 publications

References 20 publications

Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3

Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3

Prognostic Evaluation of CapG, Gelsolin, P‐gp, GSTP1, and Topo‐II Proteins in Non‐Small Cell Lung Cancer

Ca2+ Binding to EF Hands 1 and 3 Is Essential for the Interaction of Apoptosis-Linked Gene-2 with Alix/AIP1 in Ocular Melanoma

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Ca²⁺ Binding to EF Hands 1 and 3 Is Essential for the Interaction of Apoptosis-Linked Gene-2 with Alix/AIP1 in Ocular Melanoma