Overexpression of cyclin B1 in human colorectal cancers

Wang, Aijin; Yoshimi, Naoki; Ino, Natsuko; Tanaka, Takuji; Mori, Hideki

doi:10.1007/bf01269891

Cited by 117 publications

(70 citation statements)

References 14 publications

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“…With similar high frequency, overexpression of cyclin B1 has been detected in adenocarcinomas of the colon. 21,38 In contrast, several human malignancies including prostate, 23 gastric, 25 lung, 39 tongue 28 and esophageal 27 cancer were frequently found to demonstrate lower immunohistochemical positivity for cyclin B1. Moreover, in several cancers high levels of cyclin B1 protein were found to be significantly associated with cancer progression, thus indicating dysregulation of cyclin B1 as a common phenomenon occurring during cancer development.…”

Section: Discussionmentioning

confidence: 99%

Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

Ikuerowo

Kuczyk

Mengel

et al. 2006

Intl Journal of Cancer

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Cyclin B1, identified as a regulator of late cell cycle, is involved in the development and progression of a variety of human malignancies. To clarify the role of cyclin B1 in the pathogenesis and prognosis of renal cell carcinoma (RCC), protein expression was compared with clinicopathological characteristics of patients as well as the long-term survival after surgical therapy. Expression analysis was carried out by immunohistochemistry and tissue microarray analysis. The microarrays that represented the primary tumors, their invasion front and normal peritumoral renal parenchyma contained 753 tissue cores obtained from 251 randomly selected nephrectomy specimens. Immunopositivity within the primary tumors was significantly associated with tumor stage (pT) (p < 0.01), lymph node status (pN) (p < 0.01) as well as the presence of systemic metastatic disease (p 5 0.01). Subcellular expression in the cytoplasm of tumor cells significantly correlated with pT (p 5 0.02) and pN (p 5 0.03). When peritumoral tissue samples exhibited a relative amount of <10% of positively reacting epithelial cells, cyclin B positivity was identified to predict long-term survival of patients in univariate analysis (p < 0.01) whereas borderline significance was observed in multivariate statistical analysis (p 5 0.05). Increased intratumoral cyclin B1 positivity and aberrant localization of signals within the cytoplasm of tumor cells is positively correlated with the tendency towards tumor progression, indicating the significant role of cyclin B1 in the development and pathogenesis of RCC. The result of uni-and multivariate statistical analysis suggests the prognostic value of cyclin B1 for RCC patients. ' 2006 Wiley-Liss, Inc.Key words: renal cell carcinoma; cyclin B1; prognosis Renal cell carcinoma (RCC), accounts for 3% of human malignancies in western countries. 1 The incidence of RCC has increased during the past decades, at least in part due to the widespread availability of imaging modalities such as ultrasonography or computerized tomography during evaluation of abdominal and gastrointestinal complaints, thus resulting in a higher frequency of incidentally diagnosed, but still organ-confined tumors. 2 Though surgery offers the chance to cure localized disease, therapy for metastatic disease remains inadequate. 3 While RCC can be considered as widely resistant towards chemo-and radiotherapy, the application of systemic immunotherapy results in a limited and in most cases disappointing clinical response. However, both a better understanding of molecular processes involved in carcinogenesis 3 as well as the introduction of molecular-targeted agents are expected to improve the efficacy of future treatment modalities that can be offered to patients with metastasized RCC. [4][5][6][7][8][9] Uncontrolled cell division is one of the key features of tumor cells. Cyclins and cyclin-dependent kinases (cdk) play an important role in the passage of cells through the cell cycle. 10,11 The early phase of the cell cycle that includes the G1 and S ...

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Section: Discussionmentioning

confidence: 99%

Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

Ikuerowo

Kuczyk

Mengel

et al. 2006

Intl Journal of Cancer

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“…Numerous studies, based on by immunochemistry or Western blot analysis, have previously reported the accumulation of cyclin B1 in malignant tumors such as colorectal and lung cancers (Wang et al, 1997;Soria et al, 2000) but the molecular mechanism underlying this deregulation have not been characterized. Our results show that accumulation of the cyclin B1 protein can be detected in the absence of mRNA overexpression or point mutations suggesting a post-translational deregulation.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of B-type cyclins alters chromosomal segregation

et al. 2002

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To identify genes which overexpression results into chromosomal instability (CIN), we developed a biological approach based on a yeast indicator strain in which CIN can be detected by a sectoring phenotype. Screening in this strain of a yeast genomic library cloned into a high copy vector led us to identify, among the clones generating 100% of sectoring colonies, Clb5, one of the six B-type cyclins present in yeast. Overexpression of cyclin B2 and cyclin B1, the two human homologs of Clb5, in the CIN indicator strain resulted also into a sectoring phenotype and induced, like overexpression of Clb5, an abnormal sensitivity to benomyl, indicating that overexpression of B-type cyclins alters the spindle checkpoint. In a series of 38 primary colorectal cancers, we detected in ®ve tumors (13%) an accumulation of cyclin B1, which was neither related to mRNA overexpression nor to mutation within the coding region, and in ®ve other tumors (13%) a 2 ± 10-fold increase of cyclin B2 mRNA which was not related to gene ampli®cation. These results suggest that overexpression of cyclins B, resulting from di erent mechanisms, could contribute, through an alteration of the spindle checkpoint, to the chromosomal instability observed in cancer.

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“…This ligase controls the degradation of Cyclin B1 (Toby et al, 2003), projecting elevated levels of this cyclin in CCNB1IP1-deficient cells. Overexpression of Cyclin B1, in turn, has been reported in various human tumors, and it is a predictor of poor prognosis (Wang et al, 1997;Soria et al, 2000;Dong et al, 2002;Hassan et al, 2002;Yasuda et al, 2002). High levels of Cyclin B1 might cause misregulation of the Cyclin B1/Cdk1 complex, allowing escape from the G2-M checkpoint induced by DNA damage (Lobrich and Jeggo, 2007).…”

Section: Discussionmentioning

confidence: 99%

Alterations of ubiquitin ligases in human cancer and their association with the natural history of the tumor

et al. 2009

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Protein ubiquitination is critical for many cellular processes, through its ability to regulate protein degradation and various signaling mechanisms. In the ubiquitin (Ub) system, substrate specificity is achieved through the E3 family of Ub ligases. Because alterations of the ubiquitination machinery have been reported in human cancers, the selective interference with Ub ligases might represent a powerful therapeutic tool. Here, we report the first wide survey of misregulation of Ub ligases in cancer. We analysed 82 Ub ligases in nine types of cancer by in situ hybridization on tissue microarrays. We found 27 instances in which an Ub ligase was altered in a given type of tumor, when compared with normal tissues: 21 cases of overexpression and 6 cases of underexpression. We further analysed selected Ub ligases in large cohorts of breast and non-small-cell lung carcinomas. In five, of six, of these extended analyses (HUWE1, CCNB1IP1, SIAH1 and SIAH2 in breast cancer and CCNB1IP1 in lung cancer), we found that the levels of Ub ligases correlated significantly with relevant prognostic factors, and with clinical outcome. Our findings show that the alteration of Ub ligases is a frequent event in cancer and identify candidate targets for molecular therapies.

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Overexpression of cyclin B1 in human colorectal cancers

Cited by 117 publications

References 14 publications

Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

Overexpression of B-type cyclins alters chromosomal segregation

Alterations of ubiquitin ligases in human cancer and their association with the natural history of the tumor

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