Centrosome abnormalities are frequently observed in non‐small‐cell lung cancer and are associated with aneuploidy and cyclin E overexpression

Koutsami, MK; Tsantoulis, Petros; Kouloukoussa, Mirsini; Apostolopoulou, Kalliopi; Pateras, IS; Spartinou, Z; Drougou, Angeliki; Evangelou, Konstantinos; Kittas, Christos; Bártková, Jiřina; Bártek, Jiří; Gorgoulis, V.G.

doi:10.1002/path.2005

Cited by 63 publications

(62 citation statements)

References 39 publications

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“…Moreover, in human chronic human herpesvirus 8 (HHV-8) infection, purified viral proteins resulted in ␥␦ V␦1 T cell activation. 5 Taken together, we agree with Casetti et al that human ␥␦ T cells recognize nonpeptidic phosphoantigens, metabolites of the isoprenoid pathway. 6,7 However, the mechanism by which human ␥␦ T cells recognized protein antigens remains unclear currently and needs further investigation.…”

Section: Human Memory But Not Naïve ␥␦ T Cells From Tst-positive Indisupporting

confidence: 79%

“…Cyclin E provokes genomic instability, when overexpressed, by producing either DNA damage and/or centrosome amplification. 4,5 Upregulation of cyclin E is frequently observed in cancer, and is associated in various malignancies with poor survival. 6 To test this hypothesis we mimicked the above scenario by silencing Skp2 alone or in combination with p27 KIP1 in A549 cancer cells, which express high Skp2 levels.…”

Section: Is Exclusive Skp2 Targeting Always Beneficial In Cancer Thermentioning

confidence: 99%

See 1 more Smart Citation

Is exclusive Skp2 targeting always beneficial in cancer therapy?

Koutsami¹,

Velimezi²,

Kotsinas³

et al. 2008

Blood

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Response Human memory but not naïve ␥␦ T cells from TST-positive individuals respond to M tuberculosis antigenWe thank Casetti et al for their interest in our recent work, "CD4 ϩ CD25 ϩ Treg cells inhibit human memory ␥␦ T cells to produce IFN-␥ in response to M tuberculosis antigen ESAT-6." 1 In our article, we showed that stimulation of peripheral blood mononuclear cells (PBMCs) from tuberculin skin test (TST)-positive individuals with ESAT-6 resulted in not only the production of cytokines but also the activation and division of memory ␥␦ T cells. These responding ␥␦ T cells displayed the phenotype of memory but not naive ␥␦ T cells. Most interestingly, CD4 ϩ CD25 ϩ Treg cells could inhibit IFN-␥ production by ␥␦ T cells. Casetti et al observed that CD4 ϩ but not ␥␦ T cells from 4 patients with active tuberculosis (TB) disease and 4 subjects with latent TB infection (LTBI) responded to ESAT-6 to express IFN-␥. In accordance with their and others' observations, 2 in our unpublished data from a few active TB patients, we also found that CD4 ϩ T cells, in addition to ␥␦ T cells, produced IFN-␥ in response to ESAT-6. Of note, the cells from different individuals with TB infection had distinct quality of response. The discrepancies between their and our results on the response of ␥␦ T cells to ESAT-6 might be influenced by many factors. The concern might be that the source of ESAT-6 we purchased from suppliers was different from that Casetti et al used. The various preparations of recombinant antigens, including cloning, sequences, expression, and purification process from different companies, might have different biologic activities. Moreover, differences in the classical and nonclassical major histocompatibility class (MHC) molecules, the affinity to antigenic epitopes, and the distinct biologic features between eastern and western peoples might lead to distinct reactivity to the same antigen. Clearly, it has been reported that ␥␦ T cells from bovines could react to ESAT-6 by IFN-␥ production and proliferation. 3 In addition, several antigenic epitopes/proteins recognized by human ␥␦ T cells have been identified via CDR3␦ peptide-based immunobiochemical strategy. 4 These peptides not only bind to ␥␦ T cells but also activate ␥␦ T cells. Moreover, in human chronic human herpesvirus 8 (HHV-8) infection, purified viral proteins resulted in ␥␦ V␦1 T cell activation. 5 Taken together, we agree with Casetti et al that human ␥␦ T cells recognize nonpeptidic phosphoantigens, metabolites of the isoprenoid pathway. 6,7 However, the mechanism by which human ␥␦ T cells recognized protein antigens remains unclear currently and needs further investigation. Li Li and Chang-You Wu Approval was obtained from the Zhongshan School of Medicine, Sun Yat-Sen University institutional review board for these studies. Informed consent was obtained in accordance with the Declaration of Helsinki. Conflict-of-interest disclosure: The authors declare no competing financial interests.Correspondence : Changyou Wu, MD, PhD, Department of Immuno...

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Section: Human Memory But Not Naïve ␥␦ T Cells From Tst-positive Indisupporting

confidence: 79%

Section: Is Exclusive Skp2 Targeting Always Beneficial In Cancer Thermentioning

confidence: 99%

Is exclusive Skp2 targeting always beneficial in cancer therapy?

Koutsami¹,

Velimezi²,

Kotsinas³

et al. 2008

Blood

View full text Add to dashboard Cite

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“…13e16 The significance of LMW-E, which was originally discovered in breast cancer by our group and subsequently by others, 17e20 has recently been the subject of several review articles. 21e23 These isoforms are also found in ovarian cancer, 4,24 melanomas, 2 gastric cancer, 25 colorectal cancer, 26e28 lung cancer, 29 and renal cell carcinomas 30 and are strongly associated with poor survival in patients. 4,26,31 Work from our laboratory has implicated LMW-E in breast cancer oncogenesis.…”

mentioning

confidence: 99%

Cytoplasmic Cyclin E and Phospho–Cyclin-Dependent Kinase 2 Are Biomarkers of Aggressive Breast Cancer

Karakaş

Biernacka

Bui

et al. 2016

The American Journal of Pathology

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Cyclin E and its co-activator, phosphoecyclin-dependent kinase 2 (p-CDK2), regulate G 1 to S phase transition and their deregulation induces oncogenesis. Immunohistochemical assessments of these proteins in cancer have been reported but were based only on their nuclear expression. However, the oncogenic forms of cyclin E (low molecular weight cyclin E or LMW-E) in complex with CDK2 are preferentially mislocalized to the cytoplasm. Here, we used separate nuclear and cytoplasmic scoring systems for both cyclin E and p-CDK2 expression to demonstrate altered cellular accumulation of these proteins using immunohistochemical analysis. We examined the specificity of different cyclin E antibodies and evaluated their concordance between immunohistochemical and Western blot analyses in a panel of 14 breast cell lines. Nuclear versus cytoplasmic staining of cyclin E readily differentiated fulllength from LMW-E, respectively. We also evaluated the expression of cyclin E and p-CDK2 in 1676 breast carcinoma patients by immunohistochemistry. Cytoplasmic cyclin E correlated strongly with cytoplasmic p-CDK2 (P < 0.0001), high tumor grade, negative estrogen/progesterone receptor status, and human epidermal growth factor receptor 2 positivity (all P < 0.0001). In multivariable analysis, cytoplasmic cyclin E plus phosphorylated CDK2 (as one variable) predicted breast cancer recurrence-free and overall survival. These results suggest that cytoplasmic cyclin E and p-CDK2 can be readily detected with immunohistochemistry and used as clinical biomarkers for aggressive breast cancer. (Am J Pathol 2016 http://dx

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“…Numerical and functional abnormalities of centrosomes result in an increase in aberrant mitotic spindle formation, merotelic kinetochore-microtubule attachment errors, lagging chromosome formation, and chromosome segregation errors, all of which are thought to be possible causes of chromosome instability (Ganem et al, 2009;Nigg & Raff, 2009). Centrosome abnormalities and chromosome instability are characteristics of human lung cancer (Masuda and Takahashi, 2002;Koutsami et al, 2006;Jung et al, 2007;Shinmura et al, 2008), and abnormalities in genes responsible for centrosome regulation have been reported in lung cancer (Fukasawa, 2007;Lee et al, 2010). In this Review, the status of centrosome abnormalities in lung cancer, the mechanisms responsible for inducing centrosome abnormalities, and the relationship between centrosome abnormalities and chromosome instability are summarized.…”

Section: Introductionmentioning

confidence: 99%