DNA-synthesizing enzymes in breast cancer (thymidine kinase, thymidylate synthase and thymidylate kinase): Association with flow cytometric s-phase fraction and relative prognostic importance in node-negative premenopausal patients

Romain, Sylvie; Bendahl, Pär Ola; Guirou, O.; Malmström, Per; Martin, Pierre Marie; Fernö, Mårten

doi:10.1002/1097-0215(20010120)95:1<56::aid-ijc1010>3.0.co;2-3

Cited by 20 publications

(9 citation statements)

References 34 publications

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“…Samples with receptor content ⩾20 fmol mg –1 protein were classified as oestrogen receptor or PR positive. Cut-offs corresponding to the seventy-fifth percentiles in the distributions were used to dichotomise UPA, PAI-1 (Bouchet et al , 1999) and TK (Romain et al , 1995, 2000, 2001) as previously recommended.…”

Section: Methodsmentioning

confidence: 99%

Epstein-Barr virus as a marker of biological aggressiveness in breast cancer

et al. 2010

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Purpose:Although a potential role of the Epstein-Barr virus (EBV) in the pathogenesis of breast cancer (BC) has been underlined, results remain conflicting. Particularly, the impact of EBV infection on biological markers of BC has received little investigation.Methods:In this study, we established the frequency of EBV-infected BC using real-time quantitative PCR (RT–PCR) in 196 BC specimens. Biological and pathological characteristics according to EBV status were evaluated.Results:EBV DNA was present in 65 of the 196 (33.2%) cases studied. EBV-positive BCs tended to be tumours with a more aggressive phenotype, more frequently oestrogen receptor negative (P=0.05) and with high histological grade (P=0.01). Overexpression of thymidine kinase activity was higher in EBV-infected BC (P=0.007). The presence of EBV was weakly associated with HER2 gene amplification (P=0.08).Conclusion:Our study provides evidence for EBV-associated BC undergoing distinct carcinogenic processes, with more aggressive features.

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Section: Methodsmentioning

confidence: 99%

Epstein-Barr virus as a marker of biological aggressiveness in breast cancer

et al. 2010

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“…The processing and pathologic examination of the tumors were performed as previously described. 22,23 Briefly, uPA and PAI-1 levels were analyzed in cytosolic tumor extracts by means of an enzyme-linked immunosorbent assay (Immunobinds ELISA Kit, American Diagnostic, Greenwich, CT USA). Steroid hormone receptors (estrogen receptor-progesterone receptor) were initially determined biochemically in cytosol fractions and then expressed quantitatively (fmol/mg protein) (Abbott Laboratories, Diagnostic Division, Chicago, IL).…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

Prognostic significance of tumor-related proteases as a function of the estrogen receptor status

Mazouni¹,

Romain²,

Bonnier³

et al. 2011

Cancer Biology & Therapy

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IntroductionEstrogen receptor (ER) determination is a standard tool used to evaluate the prognosis of breast cancer (BC) and progesterone receptor (PgR) expression, which is determined at the same time, can reflect ER functionality.1 However, simply ascertaining the ER and PgR status might be insufficient to accurately appraise the prognosis of patients or their ability to respond to treatment. 2Some other indicators recently recognized as prognostic factors 3 will probably be included in the near future as routine parameters for personalized therapeutics. In particular, those proteins that reflect the functional integrity of the estrogen response pathway could be useful.Proteases and their inhibitors have been a subject of interest in BC since they were demonstrated to play a role in invasiveness, tumor spread and metastatic processes. [4][5][6][7] Particularly during the last years, two serine proteases, urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1), were recognized, with level of evidence I (LOE I), as biomarkers of the prognosis, in the recent panel expert consensus.3 These proteases are involved in collagenase IV destruction and the degradation of the basement membrane and therefore promote the metastatic process. 8,9Background: Tumor-related proteases such as urokinase-type plasminogen (upa), plasminogen activator inhibitor (paI-1) and cathepsin D (cath-D) are involved in the prognosis of breast cancer (BC) and promote the metastatic process. We investigated the relationship between these proteases and their prognostic significance according to the eR status.Results: Quantitative levels of upa and paI-1 were higher in eR -patients (p < 0.001) whereas no difference was observed for cath-D levels in eR subsets (p = 0.96). In patients with a positive and highly positive eR status, a high cath-D level was associated with a poorer prognosis. patients in the highly positive eR group experienced poorer survival in the group with a high paI-1 level compared to the group with a low paI-1 level. In eR + patients, cath-D (p = 0.02) and the tumor size (p = 0.03) were independent factors for Os.Methods: upa, paI-1 and cath-D levels were prospectively measured in tumor from 316 patients with primary BC. The distribution and relationship between these proteases and eR subsets were analyzed as well as the prognostic significance.Conclusion: The prognostic significance of proteases is modulated by the eR status. Cath-D and paI-1 could identify a high-risk group with an adverse outcome in eR + patients.

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“…NAMI-A and RAPTA-T caused a significant upregulation of Omega-amidase (NIT2) [32], Thymidylate kinase (TMK) [33], Histidine triad nucleotide-binding protein 1 (HINT1) [34], and Prefoldin subunit 3 (PFD3) [35] while DNA polymerase epsilon subunit 3 (POLE3) [36] was markedly downregulated. In addition, exposure to NAMI-A induced a significant upregulation of serine threonine protein phosphatase subunit b (PP2A) [37], peptidylprolyl cis-trans isomerase D (PPID), elongation factor 1-delta (EF1D) [38], cathepsin D (CATD) [39], peroxiredoxin-1 (PRDX1) [40] and protein S100-A4 (S10A4); while exposure to RAPTA-T caused upregulation of acetyl-CoA acetyltransferase [41], cytosolic (ACAT2), deoxyuridine 5′-triphosphate nucleotidohydrolase-mitochondrial-(DUT) and ubiquitinconjugating enzyme E2 G1.…”

Section: Proteomic Profiles Of Treated and Control Cellsmentioning

confidence: 99%