Expression of cell cycle regulatory proteins in the multistep process of oesophageal carcinogenesis: stepwise over-expression of cyclin E and p53, reduction of p21WAF1/CIP1 and dysregulation of cyclin D1 and p27KIP1

2001 ◽  
Vol 39 (6) ◽  
pp. 589-596 ◽  
Author(s):  
M Ohbu ◽  
N Kobayashi ◽  
I Okayasu
1999 ◽  
Vol 189 (2) ◽  
pp. 186-193 ◽  
Author(s):  
Wolfram M�ller ◽  
Tsuyoshi Noguchi ◽  
Hans-Christian Wirtz ◽  
Gerhard Hommel ◽  
Helmut E. Gabbert

1998 ◽  
Vol 29 (11) ◽  
pp. 1304-1309 ◽  
Author(s):  
Songtao Wang ◽  
Joanne Wuu ◽  
Lou Savas ◽  
Nilima Patwardhan ◽  
Ashraf Khan

2014 ◽  
Vol 121 (5) ◽  
pp. 1189-1200 ◽  
Author(s):  
Min Soo Kim ◽  
Kyu Hong Kim ◽  
Eun Hee Lee ◽  
Young Min Lee ◽  
Sung-Hun Lee ◽  
...  

Object The aim of this study was to evaluate the role of certain cell-cycle regulatory proteins in the recurrence of atypical meningiomas. These proteins were analyzed with immunohistochemical staining to identify predisposing factors for the recurrence of atypical meningiomas. Methods The authors retrospectively reviewed the medical records of patients with atypical meningiomas diagnosed in the period from January 2000 to June 2012 at the Department of Neurosurgery at Samsung Changwon Hospital and Dong-A University Medical Center. Clinical data included patient sex and age at the time of surgery, presenting symptoms at diagnosis, location and size of tumor, extent of surgery, use of postoperative radiotherapy, duration of follow-up, and recurrence. Immunohistochemical staining for cell-cycle regulatory proteins (p16, p15, p21, p27, cyclin-dependent kinase [CDK] 4 and 6, phosphorylated retinoblastoma [pRB] protein, and cyclin D1) and proliferative markers (MIB-1 antigen, mitosis, and p53) was performed on archived paraffin-embedded tissues obtained during resection. The recurrence rate and time to recurrence were assessed using Kaplan-Meier analysis. Results Of the 67 atypical meningiomas eligible for analysis, 26 (38.8%) recurred during the follow-up period (mean duration 47.7 months, range 8.4–132.1 months). Immunohistochemically, there was overstaining for p16 in 44 samples (65.7%), for p15 in 21 samples (31.3%), for p21 in 25 samples (37.3%), for p27 in 32 samples (47.8%), for CDK4 in 38 samples (56.7%), for CDK6 in 26 samples (38.8%), for pRB protein in 42 samples (62.7%), and for cyclin D1 in 49 samples (73.1%). Multivariate analysis using the Cox proportional-hazards regression model showed that incomplete resection (HR 4.513, p < 0.001); immunohistochemical understaining for p16 (HR 3.214, p < 0.001); immunohistochemical overstaining for CDK6 (HR 3.427, p < 0.001), pRB protein (HR 2.854, p = 0.008), and p53 (HR 2.296, p = 0.040); and increased MIB-1 labeling index (HR 2.665, p = 0.013) and mitotic index (HR 2.438, p = 0.024) predicted the recurrence of atypical meningiomas after resection. Conclusions Findings in this study indicated that p16, CDK6, and pRB protein were associated with the recurrence of atypical meningiomas.


2003 ◽  
Vol 31 (04) ◽  
pp. 563-572 ◽  
Author(s):  
Hyun-A Kim ◽  
Hyung-Keun You ◽  
Hyung-Shik Shin ◽  
Youn-Chul Kim ◽  
Tai-Hyun Kang ◽  
...  

Sophorae Radix, the dried roots of Sophora flavescens AITON (Leguminosae), has been used in Oriental traditional medicine for treatment of skin and mucosal ulcers, sores, gastrointestinal hemorrhage, diarrhea, inflammation and arrhythmia. In the present study, we examine the effect of the aqueous extract of Sophorae Radix (AESR) on cell proliferation and cell cycle regulation in human oral mucosal fibroblasts (HOMFs). To study the molecular mechanisms of cell cycle regulation by AESR, we also measured the intracellular levels of cell cycle regulatory proteins such as cyclin D, cyclin-dependent kinases (CDK)-4, CDK-6, cyclin E, CDK-2, p53, p21WAF1/CIP1 and p16INK4 . Cell proliferation was increased in the presence of 10~500 μg/ml of AESR. Maximal growth stimulation was observed in those cells exposed to 100 μg/ml of AESR. Exposure of HOMFs to 100 μg/ml of AESR resulted in an increase of cell cycle progression. The levels of cyclin E and CDK-2 were increased in HOMFs after 100 μg/ml of AESR treatment, but the levels of cyclin D, CDK-4, and CDK-6 were unchanged. After exposure to 100 μg/ml of AESR, the protein levels of p16INK4A and p53 were decreased as compared to that of the control group, but the level of p21WAF1/CIP1 was similar in the cells treated with 100 μg/ml of AESR and untreated cells. The results suggest that AESR may increase cell proliferation and cell cycle progression in HOMFs, which is linked to increased cellular levels of cyclin E and CDK-2 and decreased cellular levels of p53 and p16INK4A . Further studies are necessary to clarify the active constituents of AESR responsible for such biomolecular activities.


Endocrinology ◽  
2007 ◽  
Vol 149 (1) ◽  
pp. 193-207 ◽  
Author(s):  
Jinchun Yan ◽  
Terry R. Brown

Age-dependent epithelial cell hyperplasia in the dorsal and lateral lobes of Brown Norway rats is analogous to benign prostatic hyperplasia in aging men. A major question is whether differential lobe-specific and age-dependent proliferation of cells, rather than cell survival, contributes to the hyperplasia. Although serum testosterone (T) levels decline in aged rats, active cell proliferation was detected as Ki67-positive cells in the dorsal and lateral lobes. We determined whether androgens differentially affect cell proliferation and cell-cycle regulatory proteins in the prostate lobes of young and aged rats. Castrated rats were treated with different doses of T to restore serum levels to those of intact young or aged rats. Rates of cell proliferation, measured by 5-bromodeoxyuridine labeling, peaked after 3-d T treatment in all lobes. 5-bromodeoxyuridine-labeling indices were higher in the dorsal and lateral lobes of aged than of young rats with equivalent serum T levels. No age-dependent difference was seen in the ventral lobe. Cell proliferation was marked by increased levels of cyclins D1 and E and cyclin-dependent kinases 4 and 6, decreased p27 and increased phosphorylation of Rb. Levels of cyclins D1 and E were higher in the dorsal and lateral lobes of intact and T-treated aged than young rats. Confocal immunofluorescent microscopy documented changes in cyclin-dependent kinase 4 and cyclin D1 subcellular localization. Cyclin D1 nuclear localization correlated with the time frame for cell proliferation. In conclusion, rates of cell proliferation and levels of cell-cycle regulatory proteins that control the G1/S transition exhibit lobe-specific and age-dependent differences in response to androgens.


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