Cyclin B1, unlike cyclin G1, increases significantly during colorectal carcinogenesis and during later metastasis to lymph nodes

Li, Jiaqing; Kubo, Akihito; Wu, Fei; Usuki, Hisashi; Fujita, Jiro; Bandoh, Shuji; Masaki, Tsutomu; Saoo, Kousuke; Takeuchi, Hijiri; Kobayashi, Shōji; Imaida, Katsumi; Maeta, Hajime; Ishida, Toshihiko; Kuriyama, Shigeki

doi:10.3892/ijo.22.5.1101

Cited by 26 publications

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“…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. 6,27,36,40 Additionally, in our study cytoplasmic accumulation of cyclin B1 was significantly associated with an increased tendency of RCC towards tumor progression, which is similar to recent findings in breast cancer. 17 A possible mechanism that could explain this observation is that cytoplasmic accumulation of cyclin B1 in tumor cells favors the premature entry into mitosis by overriding a p53-mediated G2/M checkpoint, thus promoting uncontrolled cellular proliferation and disease progression.…”

Section: Discussionsupporting

confidence: 80%

“…These results are in concordance with previous reports, which demonstrated that cyclin B1 expression is reduced in the invasive margin tissues of colorectal carcinoma, thus indicating reduced cellular proliferation. 6,29 Regarding the prognosis of RCC patients, we again found no association with expression of cyclin B1 in the invasion front tissue specimens.…”

Section: Discussionmentioning

confidence: 62%

“…6,25 No correlation with clinicopathological variables or the patients' long-term survival was observed in studies investigating colon, 21 gastric 45 and prostate 46 cancers. Therefore, organ specificity or heterogeneity of the expression of cyclin B1 may specifically affect tumor progression and clinical prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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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: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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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 overexpression is also observed in various carcinomas, including esophageal squamous cell carcinoma, laryngeal squamous cell carcinoma and colorectal carcinoma. [26][27][28][29] In the present study, cyclin G1 overexpression increased cyclin B1 expression, accompanied with increased CDC2 kinase activity with or without radiation, whereas the expression of p21, which is known as a broad range CDK inhibitor, was downregulated, suggesting inhibition of radiation-induced G2 arrest by cyclin G1. Because cyclin B1 expression by cyclin G1 was transcriptionally regulated (Figure 7), we suggest that increased cyclin B1 by cyclin G1 may be involved in CDC2 kinase activity with no change of CDC2 protein level, downregulation of p21 protein level, and finally inhibiting G2 arrest.…”

Section: Discussionsupporting

confidence: 49%

Cyclin G1 overcomes radiation-induced G2 arrest and increases cell death through transcriptional activation of cyclin B1

Seo

Lee

et al. 2005

Cell Death Differ

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Although cyclin G1 has been implicated in certain p53-related biological phenomena, other aspects of its function remain unclear. Here we report hitherto unknown mechanism by which cyclin G1 increases radiation sensitivity by regulating the level of cyclin B1. Overexpression of cyclin G1 was observable in lung carcinoma tissues. Irradiation of human lung cells with cyclin G1 overexpression resulted in increased cell death and c-H2AX foci suggesting that cyclin G1 rendered the cells more susceptible to DNA damage. Enhanced radiosensitivity by cyclin G1 was correlated with increased cyclin B1, CDC2/cyclin B1 complex, and MPM2. Cell cycle synchronization clearly showed coexpression of cyclin G1 and cyclin B1 in G2/M phase. Depletion of cyclin G1 by interference RNA revealed that cyclin G1 regulated transcription of cyclin B1 in a p53-independent manner, and confirmed that the increased mitotic cells and cell death by cyclin G1 were dependent upon cyclin B1. Therefore, our data suggest that cyclin G1 enhanced radiation sensitivity by overriding radiation-induced G2 arrest through transcriptional upregulation of cyclin B1.

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SPARC expression induces cell cycle arrest via STAT3 signaling pathway in medulloblastoma cells

Chetty

Dontula

Nagaraju

et al. 2012

Biochemical and Biophysical Research Communications

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Dynamic cell interaction with ECM components has profound influence in cancer progression. SPARC is a component of the ECM, impairs the proliferation of different cell types and modulates tumor cell aggressive features. We previously reported that SPARC expression significantly impairs medulloblastoma tumor growth in vivo. In this study, we demonstrate that expression of SPARC inhibits medulloblastoma cell proliferation. MTT assay indicated a dose-dependent reduction in tumor cell proliferation in adenoviral mediated expression of SPARC full length cDNA (Ad-DsRed-SP) in D425 and UW228 cells. Flow cytometric analysis showed that Ad-DsRed-SP-infected cells accumulate in the G2/M phase of cell cycle. Further, immunoblot and immunoprecipation analyses revealed that SPARC induced G2/M cell cycle arrest was mediated through inhibition of the Cyclin-B-regulated signaling pathway involving p21 and Cdc2 expression. Additionally, expression of SPARC decreased STAT3 phosphorylation at Tyr-705; constitutively active STAT3 expression reversed SPARC induced G2/M arrest. Ad-DsRed-SP significantly inhibited the pre-established orthotopic tumor growth and tumor volume in nude-mice. Immunohistochemical analysis of tumor sections from mice treated with Ad-DsRed-SP showed decreased immunoreactivity for pSTAT3 and increased immunoreactivity for p21 compared to tumor section from mice treated with mock and Ad-DsRed. Taken together our studies further reveal that STAT3 plays a key role in SPARC induced G2/M arrest in medulloblastoma cells. These new findings provide a molecular basis for the mechanistic understanding of the effects of SPARC on medulloblastoma tumor cell proliferation.

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Cyclin B1, unlike cyclin G1, increases significantly during colorectal carcinogenesis and during later metastasis to lymph nodes

Cited by 26 publications

References 0 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

Cyclin G1 overcomes radiation-induced G2 arrest and increases cell death through transcriptional activation of cyclin B1

SPARC expression induces cell cycle arrest via STAT3 signaling pathway in medulloblastoma cells

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