High-Level SLP-2 Expression and HER-2/neu Protein Expression Are Associated With Decreased Breast Cancer Patient Survival

Cao, Weijun; Zhang, Bin; Liu, Yanxue; Li, Hongtao; Zhang, Shiwu; Fu, Li; Niu, Yun; Ning, Lu; Cao, Xuchen; Liu, Zhihua; Sun, Baocun

doi:10.1309/c6x54hrb580ep2nq

Cited by 42 publications

(46 citation statements)

References 14 publications

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“…Intriguingly, subset #4 patients consistently exhibited a lower expression of the genes identified. Detailed characterization of the differently expressed genes in biological processes, using alternative approaches such as gene ontology tree machine and ingenuity pathway analysis, revealed that these genes are involved in cell cycle control and proliferation, such as STOML2 and PPP2CA, 21,22 suggesting that these tumors have a low proliferative capacity compared to other CLL subsets, including subset #16. 29 This is supported by the identification of a subset of genes involved in hematopoiesis as well as humoral and cellmediated immune responses (Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…Briefly, we found significant overrepresentation of genes affecting proliferation, cell cycle control and regulation of transcription activity including STOML2, PPP2CA and HOXA1. [21][22][23] To further analyze our data, a second search using ingenuity pathway analysis was performed, again focusing on genes that differed in expression between subset #4 and subset #16, and identified a number of gene networks which were significantly enriched. These were classified as follows and are listed in Table 3: (i) cellular growth and proliferation (16 genes); (ii) humoral immune response (12 genes); (iii) cell-mediated immune response (13 genes); and (iv) hematopoiesis (7 genes).…”

Section: Biological Annotation Of Identified Genesmentioning

confidence: 99%

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Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors

Marincevic¹,

Mansouri²,

Kanduri³

et al. 2010

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundNumerous subsets of patients with chronic lymphocytic leukemia display similar immunoglobulin gene usage with almost identical complementarity determining region 3 sequences. Among IGHV4-34 cases, two such subsets with "stereotyped" B-cell receptors were recently identified, i.e. subset #4 (IGHV4-34/IGKV2-30) and subset #16 (IGHV4-34/IGKV3-20). Subset #4 patients appear to share biological and clinical features, e.g. young age at diagnosis and indolent disease, whereas little is known about subset #16 at a clinical level. Design and MethodsWe investigated the global gene expression pattern in sorted chronic lymphocytic leukemia cells from 25 subset/non-subset IGHV4-34 patients using Affymetrix gene expression arrays. ResultsAlthough generally few differences were found when comparing subset to non-subset 4/16 IGHV4-34 cases, distinct gene expression profiles were revealed for subset #4 versus subset #16. The differentially expressed genes, predominantly with lower expression in subset #4 patients, are involved in important cell regulatory pathways including cell-cycle control, proliferation and immune response, which may partly explain the low-proliferative disease observed in subset #4 patients. ConclusionsOur novel data demonstrate distinct gene expression profiles among patients with stereotyped IGHV4-34 B-cell receptors, providing further evidence for biological differences in the pathogenesis of these subsets and underscoring the functional relevance of subset assignment based on B-cell receptor sequence features.Key words: stereotyped BCR, IGHV4-34, chronic lymphocytic leukemia, gene expression. IGHV4-34 B-cell receptors. Haematologica 2010;95(12):2072-2079. doi:10.3324/haematol.2010 This is an open-access paper. © F e r r a t a S t o r t i F o u n d a t i o n Citation: Marincevic M, Mansouri M, Kanduri M, Isaksson A, Göransson H, Smedby KE, Jurlander J, Juliusson G, Davi F, Stamatopoulos K, and Rosenquist R. Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors

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Section: Discussionmentioning

confidence: 99%

Section: Biological Annotation Of Identified Genesmentioning

confidence: 99%

Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors

Marincevic¹,

Mansouri²,

Kanduri³

et al. 2010

Haematologica

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“…paratarg-7. Sequence analysis revealed that paratarg-5 was identical to microtubule-associated protein, paratarg-6 to LAPTM5 and paratarg-7 to STOML2 (stomatin [EPB72]-like), also known as HSPC108 or stomatin-like-protein, which is expressed in all human tissues and has been reported to be overexpressed 11,12 and related to cell growth in several cancer, 13 while other investigators found that it modulates T-cell activation. 14 To confirm this relative high frequency of paratarg-7 recognition by paraproteins, a second series of additional 89 paraproteincontaining sera (24 IgA, 65 IgG) were not screened for reactivity with the entire spectrum of 37,200 clones represented on the macroarray, but were tested together with the first 103 paraproteincontaining sera at a dilution of 1 3 10 8 for antiparatarg-7 reactivity only using both the paratarg-7 immunoblot assay and paratarg-7 ELISA.…”

Section: Identification Of Paraprotein-binding Clonesmentioning

confidence: 99%

A frequent target of paraproteins in the sera of patients with multiple myeloma and MGUS

Preuss

Pfreundschuh

Ahlgrimm

et al. 2009

Intl Journal of Cancer

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Antigenic targets of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) paraproteins might play a role in the pathogenesis of these neoplasms. We screened a human fetal brain-derived macroarray with the IgA or IgG containing sera of 192 consecutive MGUS and MM patients. Twenty-nine of 192 (15.1%) paraproteins reacted with paratarg-7, a protein of unknown function which is expressed in all human tissues. Paratarg-7 reactivity was similarly frequent among IgA and IgG paraproteins, but all paratarg-7 reactive IgG paraproteins belonged to the IgG3 subtype with 24/57 IgG3 (42.1%) paraproteins displaying this specificity. Sequence analysis of paratarg-7 derived from patients having a paraprotein with specificity for paratarg-7 revealed no differences to paratarg-7 derived from patients with paraproteins of other specificities or healthy controls, excluding mutations or polymorphisms as a reason for its autoimmunogenicity. Similarly, Western-blot analysis showed identical bands for paratarg-7 derived from patients and controls. The above-random frequency of paratarg-7 as a paraprotein target suggests that paratarg-7 might be involved in the development of the respective clonal proliferations. The identification of paratarg-7 as an antigenic target enables the more detailed analysis of tumor-host interactions in these patients and their role in the pathogenesis of MM and MGUS. ' 2009 UICC

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“…Phylogenic analysis revealed that SLP-2 was acquired through the mitochondrial endosymbiosis and belongs to a different lineage than other stomatin-like proteins [21]. SLP-2 is highly expressed in several types of human tumors [22], and high SLP-2 levels are associated with decreased survival of patients suffering from primary invasive breast cancer [23], suggesting a role for SLP-2 in tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

SLP-2 negatively modulates mitochondrial sodium–calcium exchange

et al. 2010

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a b s t r a c tMitochondria play a major role in cellular calcium homeostasis. Despite decades of studies, the molecules that mediate and regulate the transport of calcium ions in and out of the mitochondrial matrix remain unknown. Here, we investigate whether SLP-2, an inner membrane mitochondrial protein of unknown function, modulates the activity of mitochondrial Ca 2+ transporters. In HeLa cells depleted of SLP-2, the amplitude and duration of mitochondrial Ca 2+ elevations evoked by agonists were decreased compared to control cells. SLP-2 depletion increased the rates of calcium extrusion from mitochondria. This effect disappeared upon Na + removal or addition of CGP-37157, an inhibitor of the mitochondrial Na + /Ca 2+ exchanger, and persisted in permeabilized cells exposed to a fixed cytosolic Na + and Ca 2+ concentration. The rates of mitochondrial Ca 2+ extrusion were prolonged in SLP-2 over-expressing cells, independently of the amplitude of mitochondrial Ca 2+ elevations. The amplitude of cytosolic Ca 2+ elevations was increased by SLP-2 depletion and decreased by SLP-2 over-expression. These data show that SLP-2 modulates mitochondrial calcium extrusion, thereby altering the ability of mitochondria to buffer Ca 2+ and to shape cytosolic Ca 2+ signals.

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High-Level SLP-2 Expression and HER-2/neu Protein Expression Are Associated With Decreased Breast Cancer Patient Survival

Cited by 42 publications

References 14 publications

Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors

Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors

A frequent target of paraproteins in the sera of patients with multiple myeloma and MGUS

SLP-2 negatively modulates mitochondrial sodium–calcium exchange

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