The effect of radiation on G2 blocks, cyclin B expression and cdc2 expression in human squamous carcinoma cell lines with different radiosensitivities

Smeets, Monique; Mooren, E.H.M.; Begg, Adrian C.

doi:10.1016/0167-8140(94)90357-3

Cited by 47 publications

(28 citation statements)

References 19 publications

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“…19 However, to prevent premature mitosis following DNA damage, cyclin B1-cdk1 complexes could be retained in the cytoplasm thus leading to mitotic block. 47,48 Interestingly, we found the expression of cyclin B1 to be predominantly retained in the cytoplasm of peritumoral, histologically benign renal parenchyma, thus indicating the status of mitotically blocked cells. The finding of peritumoral cytoplasmic expression of cyclin B1 in normal colonic 21 and gastric 25 mucosa cells has also been previously described.…”

Section: Discussionmentioning

confidence: 76%

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: 76%

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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“…At 28 h after irradiation, quantitative analysis showed that the BrdUrd labeling index had returned to pretreatment levels, indicating that these cells either were proliferating (S phase) or were subject to DNA repair. It is well known that a large radiation dose results in a G 2 block ranging from 0.8-3.0 h/Gy (62,63). Flow cytometry has shown that the duration of S phase is about 8 h in the C38 tumor (unpublished results).…”

Section: Dynamics Of Radiation-induced Changes In Proliferation and Amentioning

confidence: 91%

Dynamics of Hypoxia, Proliferation and Apoptosis after Irradiation in a Murine Tumor Model

et al. 2006

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“…Ionizing radiation induces a variety of responses in eukaryotic cells including cell division delay and DNA repair (1,2). In mammalian cells, this division delay may have several components including G1 arrest, S phase delay, and G2 arrest (3).…”

Section: Introductionmentioning

confidence: 99%

Transient suppression of nuclear Cdc2 activity in response to ionizing radiation

Kim

Lee²,

Lee³

2008

Oncol Rep

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Abstract. Suppression of Cdc2 activity is essential for DNA damage-induced G2 arrest. In the present study, we elucidated regulatory mechanism of Cdc2 activity during radiation-induced transient G2 arrest. Exposure of the cells to γ-radiation (4 Gy) led to a transient increase of cells in G2 at 12 h rather than M phase and then the cells resumed cell cycle progression from the G2 arrest. However, the levels of cyclin B1 and Cdc2 activity were increased in the whole cell extracts at 12 h. Despite cyclin B1 induction and increased level of Cdc2 activity after irradiation the activities in the nuclear fractions were transiently decreased at 12 h and returned to control levels by 24-48 h, demonstrating transient inhibition of nuclear translocation of cyclin B1 in response to radiation. Moreover, inhibitory phosphorylation of the Cdc2 on Tyr15 and the Cdc25C on Ser216 were increased concomitant with transient G2 arrest. The level of phosphorylated Wee1 and its activity were also markedly increased at 12 h after irradiation. In addition, radiation caused nuclear accumulation of p21 CIP1/WAF1 at 12 h, resulting in increased-binding of p21 CIP1/WAF1 to Cdc2. Nuclear p21protein level and its binding to Cdc2 gradually returned to control level when the cells resumed cell cycle progression. However, total protein level of p21 CIP1/WAF1 continued to increase until 48 h after irradiation. Collectively, these results indicate that the suppression of nuclear import of cyclin B1, the induction of Wee1 kinase activity, and the transient nuclear accumulation of p21 CIP1/WAF1 may play important roles in the transient cell cycle delay in response to ionizing radiation.

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The effect of radiation on G2 blocks, cyclin B expression and cdc2 expression in human squamous carcinoma cell lines with different radiosensitivities

Cited by 47 publications

References 19 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

Dynamics of Hypoxia, Proliferation and Apoptosis after Irradiation in a Murine Tumor Model

Transient suppression of nuclear Cdc2 activity in response to ionizing radiation

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