Creatine kinase BB isoenzyme levels in tumour cytosols and survival of breast cancer patients

Zarghami, Nosratollah; Giai, M; Yu, He; Roagna, Riccardo; Ponzone, Riccardo; Katsaros, Dionyssios; Sismondi, P; Diamandis, Eleftherios P.

doi:10.1038/bjc.1996.66

Cited by 46 publications

(37 citation statements)

References 23 publications

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“…Creatine kinase braintype (CKB) is predominantly expressed in normal lung, colon and liver tissues (60). CKB is overexpressed in a wide variety of cancers, and can serve as a penitential biomarker for various human tumors (61)(62)(63). In this study, we found that the expression of CKB was progressively decreased during human bronchial epithelial carcinogenesis, and can serve as a biomarker for early detection of LSCC.…”

Section: Fig 5 the Effects Of Gstp1 Knockdown On The Apoptosis Of Bmentioning

confidence: 65%

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

Zeng

Zhang

Deng

et al. 2012

Molecular & Cellular Proteomics

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To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional changes in the carcinogenic process were selectively validated by Western blotting. Immunohistochemistry was performed to detect the expression of the three proteins in an independent set of paraffinembedded archival specimens including various stage tissues of bronchial epithelial carcinogenesis, and their ability for early detection of LSCC was evaluated by receiver operating characteristic analysis. The results showed that the combination of the three proteins could perfectly discriminate NBE from preneoplastic lesions (SM, AH and CIS) from invasive LSCC, achieving a sensitivity of 96% and a specificity of 92% in discriminating NBE from preneoplatic lesions, a sensitivity of 100% and a specificity of 98% in discriminating NBE from invasive LSCC, and a sensitivity of 92% and a specificity of 91% in discriminating preneoplatic lesions from invasive LSCC, respectively. Furthermore, we knocked down GSTP1 in immortalized human bronchial epithelial cell line 16HBE cells, and then measured their susceptibility to carcinogen benzo ( Lung cancer is the most frequently occurring malignancy with increasing incidence and is the leading cause of mortality in cancer-related deaths in China and worldwide (1, 2). Although great improvement has been made in diagnosis and treatment of lung cancer, the overall patients' survival is still very low and does not exceed 15% (3). The poor prognosis of this cancer is mainly explained by the fact that the diagnosis is generally made only at advanced stages because of the lack of reliable, early diagnostic biomarkers and the limited understanding of its carcinogenic mechanisms. Therefore, identification of biomarkers for early detection of lung cancer is mandatory, in turn leading to more effective treatment and reduction of mortality.Lung squamous cell carcinoma (LSCC) 1 originated from the bronchial epithelial cells is the most common histological type of lung cancer. It is known that carcinogenesis of LSCC is a multistage process and the result of multistep accumulation of genetic and epigenetic alterations (4). With exposure to environmental carcinogens, bronchial epithelial carcinogenesis often progresses in the following manner: hyperplasia, squamous metaplasia (SM), atypical hyperplasia (AH), cancer in situ (CIS) and invasive cancer (5). LSCC is the end-point of a whole range of morphological abnormalities that are dis-...

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Section: Fig 5 the Effects Of Gstp1 Knockdown On The Apoptosis Of Bmentioning

confidence: 65%

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

Zeng

Zhang

Deng

et al. 2012

Molecular & Cellular Proteomics

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“…It is not known if decreased expression of CKB is a consequence of losses in chromosome 14 in colon cancers. Alternately, high levels of CKB are reported for lung and breast cancer (20,21). Serum levels of CKB are increased in cancer of the lung, prostate, colon, and ovary, suggesting that it is likely to be a generic marker rather than a specific marker for colorectal cancer (22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

Altered Expression and Localization of Creatine Kinase B, Heterogeneous Nuclear Ribonucleoprotein F, and High Mobility Group Box 1 Protein in the Nuclear Matrix Associated with Colon Cancer

Balasubramani

Day²,

Schoen

et al. 2006

Cancer Research

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Identification of biomarkers could lead to the development of effective screening tests for colorectal cancer. A previous study from our laboratory showed specific alterations of nuclear structure in colon cancer. In an effort to characterize these biomarkers, protein spots were selected from separations made by two-dimensional gel electrophoresis, which were analyzed by mass spectrometry. The sequences obtained from the isolated spots revealed that they have close similarity to creatine kinase B (CKB) isoforms, heterogeneous nuclear ribonucleoprotein F (hnRNP F) and high mobility group box 1 protein (HMGB1) isoforms. To determine the expression of these proteins in colon cancer, expression was studied in 9 tumor and matched adjacent normal pairs, 5 donor colons, 16 polyps, 4 metastatic liver lesions and matched adjacent normal pairs, and 3 liver donors. CKB and hnRNP F were expressed in 78% and 89% of colon tumors, respectively. hnRNP F had a higher frequency of expression than CKB in premalignant polyps. With the establishment of differential expression of the proteins in colon cancer, their subcellular localization was analyzed. The subcellular fractions studied both showed high protein levels of hnRNP F in colon tumors compared with normal colon tissues. Surprisingly, subcellular levels of CKB were decreased in colon tumors, suggesting that the observed high CKB levels in nuclear matrix extracts are caused by the enhanced localization of CKB to the nuclear matrix during colon tumorigenesis. These results suggest an involvement of hnRNP F and CKB in colorectal cancer. Additionally, they suggest that hnRNP F is a potential marker for colorectal cancer progression. (Cancer Res 2006; 66(2): 763-9)

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“…In fact, the association between creatine metabolism and cancer has long been reported in the literature. [35][36][37][38][39][40][41][42] However, when levels of creatine content and creatine kinase activity were examined in malignant cells and tumor-bearing animals, the results are somewhat inconsistent. Some reports show increased creatine content and elevated creatine kinase activity in various human carcinoma tissues, 35,36,38,42 while some show downregulation of the creatine kinase system in malignant tissues and tumor-bearing mice.…”

Section: Altered Lipid Metabolism In Cancer Cellsmentioning

confidence: 99%

“…[35][36][37][38][39][40][41][42] However, when levels of creatine content and creatine kinase activity were examined in malignant cells and tumor-bearing animals, the results are somewhat inconsistent. Some reports show increased creatine content and elevated creatine kinase activity in various human carcinoma tissues, 35,36,38,42 while some show downregulation of the creatine kinase system in malignant tissues and tumor-bearing mice. 37,39,41,43 It is possible that the specific role of creatine shuttle in cancer is tissue and isoform specific, as several tissue-related isoforms of creatine kinase exist: muscle, mitochondrial and brain creatine kinase.…”

Section: Altered Lipid Metabolism In Cancer Cellsmentioning

confidence: 99%

GAMT joins the p53 network: Branching into metabolism

Ide¹,

Chu²,

Aaronson³

et al. 2010

Cell Cycle

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Creatine kinase BB isoenzyme levels in tumour cytosols and survival of breast cancer patients

Cited by 46 publications

References 23 publications

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

Altered Expression and Localization of Creatine Kinase B, Heterogeneous Nuclear Ribonucleoprotein F, and High Mobility Group Box 1 Protein in the Nuclear Matrix Associated with Colon Cancer

GAMT joins the p53 network: Branching into metabolism

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