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Minichromosome Maintenance (minichromosome + maintenance)
Selected AbstractsExpression of minichromosome maintenance proteins in Merkel cell carcinomaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2009T Gambichler Abstract Objective, Minichromosome maintenance (MCM) nuclear proteins have barely been employed in the diagnosis of skin malignancies. We aimed to assess whether MCM immunohistochemistry can be utilized to examine tumour proliferation in Merkel cell carcinoma (MCC). Methods, In this pilot study, we studied skin specimens of eight patients with MCC. As a control, eight patients with cutaneous malignant melanoma (MM) were included. Immunohistochemistry was performed for MCM4, MCM6, MCM7, Ki-67, p53, and p21. Results, Protein expression of MCM4 (66.0 ± 26.5% vs. 33.9 ± 22.4%; P = 0.017), MCM6 (70.9 ± 11.9 vs. 31.7 ± 22.7; P = 0.0031), and MCM7 (76.5 ± 16.4% vs. 34.9 ± 25.5%; P = 0.0013) was significantly increased in tumour cells of MCC when compared to tumour cells of MM. Ki-67 immunoreactivity was also significantly higher in MCC than in MM (28.7 ± 7.9 vs. 11.0 ± 9.2; P = 0.0012). Immunolabelling of p53 (68.6 ± 26.2 vs. 58.4 ± 28.8; P = 0.46) and p21 (40.1 ± 38.8 vs. 25.8 ± 16.1; P = 0.35) was relatively high but not significantly increased in MCC when compared to MM. Conclusion, Our preliminary data indicate that MCM immunohistochemistry may be a useful tool for the determination of tumour cell proliferation in MCC. [source] Cyclin-dependent kinase 1 plays a critical role in DNA replication control during rat liver regeneration,HEPATOLOGY, Issue 6 2009Delphine Garnier Liver regeneration is a unique process to restore hepatic homeostasis through rapid and synchronous proliferation of differentiated hepatocytes. Previous studies have shown that hepatocyte proliferation is characterized by high expression levels of the "mitotic" cyclin-dependent kinase 1 (Cdk1) during S-phase compared to other mammalian cells. In the light of findings showing that Cdk1 compensates for the loss of Cdk2 and drives S-phase in Cdk2-deficient cells derived from Cdk2 knockout mice, we took advantage of the models of liver regeneration following partial hepatectomy and primary cultures of normal rat hepatocytes to further examine the involvement of Cdk1 during DNA replication in hepatocytes and to dissect specific cell cycle regulation in hepatocytes compared to control human foreskin fibroblasts. In hepatocytes, Cdk1 exhibited a biphasic activation pattern correlating S-phase and G2/M transition, bound to cyclin A or B1 and localized to the nucleus during DNA replication. Importantly, small interfering RNA (siRNA)-mediated silencing of Cdk1 led to a strong decrease in DNA synthesis without affecting centrosome duplication. Furthermore, in hepatocytes arrested by the iron chelator O-Trensox in early S-phase prior to DNA replication, Cdk1/cyclin complexes were active, while replication initiation components such as the minichromosome maintenance 7 (Mcm7) protein were loaded onto DNA. Moreover, Mcm7 expression and loading onto DNA were not modified by Cdk1 silencing. Conversely, in fibroblasts, Cdk1 expression and activation were low in S-phase and its silencing did not reduce DNA synthesis. Conclusion: Cdk1 is essential for DNA replication downstream formation of replication initiation complexes in hepatocytes but not in fibroblasts and, as such, our data exemplify crucial differences in the cell cycle regulation between various mammalian cell types. (HEPATOLOGY 2009.) [source] Expression of minichromosome maintenance 5 protein in proliferative and malignant skin diseasesINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2007Houjun Liu Background, The entire minichromosome maintenance (MCM) family (MCM2,7) play roles in the initiation and elongation of DNA replication. Many studies have demonstrated that MCM proteins may be better indicators of a wide variety of proliferative or cancer cells in malignant tissues. Objectives, To characterize the pattern and frequency of MCM5 expression in proliferative and malignant skin diseases in comparison with those of proliferating cell nuclear antigen (PCNA). Methods, Twelve normal skin specimens, 12 specimens of psoriasis, 21 specimens of bowenoid papulosis (BP), 16 specimens of Bowen's disease (BD), 38 specimens of skin squamous cell carcinoma (SCC), and 11 specimens of basal cell carcinoma (BCC) were subjected to immunohistochemical staining for MCM5 and PCNA. Results, MCM5 protein was expressed in the lower layers of epidermis in psoriasis, while MCM5 protein were present throughout the tumor cells in BP, BD, and moderately/poorly differentiated SCC. MCM5 protein was preferentially expressed in the periphery of well-differentiated SCC or bigger nests of BCC, although some small nests of BCC seemingly showed diffuse staining patterns. The percentages of MCM5-positive cells were 15.7% in normal skin, 21.8% in psoriasis, 75.9% in BP, 83.8% in BD, 63.5% in well-differentiated SCC, 77.5% in moderately differentiated SCC, 79.8% in poorly differentiated SCC, and 21.2% in BCC in average. Well-differentiated SCC showed a significantly lower percentage of positive cells than did moderately differentiated SCC or poorly differentiated SCC. MCM5 staining basically show a similar staining pattern to that of PCNA, but more cells tended to be stained with MCM5 than with PCNA. Conclusions, Our results demonstrate pattern and frequency of MCM5 expression in various skin diseases and suggest that MCM5 may be a useful marker to detect cell proliferation in skin tissue sections. [source] Geminin predicts adverse clinical outcome in breast cancer by reflecting cell-cycle progressionTHE JOURNAL OF PATHOLOGY, Issue 2 2004Michael A Gonzalez Abstract Geminin inhibits DNA replication by preventing Cdt1 from loading minichromosome maintenance (MCM) proteins onto DNA. The present study has investigated whether the frequency of geminin expression predicts clinical outcome in breast cancer. Immunohistochemistry was used first to examine geminin expression in normal and malignant breast tissue (n = 67). Correlations with cell-cycle parameters, pathological features, and clinical outcome were then determined using an invasive breast carcinoma tissue microarray (n = 165). Breast carcinomas were scanned for mutations (n = 61) and copy number imbalances (n = 241) of the geminin gene. Finally, the cell cycle distribution of geminin in breast cancer cells was investigated in vivo and in vitro. Despite a putative tumour suppressor function, it was found that increased geminin expression is a powerful independent indicator of adverse prognosis in invasive breast cancer. Both poor overall survival (p = 0.0002) and the development of distant metastases (p = 0.005) are predicted by high geminin expression, which performs better in this patient cohort than traditional factors currently used to determine prognosis and appropriate therapy. No mutations or deletions of the geminin gene and no evidence that a high frequency of protein expression is related to gene amplification were found. It is shown that geminin is expressed from S to M phase in breast carcinoma tissue and cell lines, disappearing at the metaphase,anaphase transition. While MCM proteins identify all non-quiescent cells, geminin identifies the sub-fraction that have entered S phase, but not exited mitosis, thereby indicating the rate of cell-cycle progression. It is suggested that this explains its unexpected value as a prognostic marker in breast cancer. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] | ||||||||||