scholarly journals Cancer - dysregulation of the cell cycle and transduction of cascade signals

2021 ◽  
Vol 11 (43) ◽  
pp. 90-100
Author(s):  
Akhmad Madaminov ◽  
Akbar Khasanov ◽  
Shuhrat Khatamov ◽  
Otabek Abdurakhmonov ◽  
Anvar Amonov ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Development ◽  
Subsequent Development ◽  
Neoplastic Cell ◽  
Scientific Data ◽  
Tissue Formation ◽  
New Era ◽  
Cyclin Dependent Kinases ◽  
Cycle Regulation

Abstract According to scientific data, cancer is a very ancient disease, and along with the perfection of humanity it becomes more progressive. The development of technologies that detect molecular changes in the pathogenesis and subsequent development of carcinogenesis has led to the beginning of a new era in oncology. The cell cycle is tightly controlled by a group of protein kinases, including cyclin and cyclin-dependent kinases. These events occur in a strictly regulated time sequence supported by consistent restriction points. p53, p21, p16, retinoblastoma (and other proteins), cyclins and cyclin-related kinases repair DNA before the cell cycle enters the phase of synthesis and mitosis. Loss of regulatory activity of p53 and pRB, stable activation of E2F stimulates uncontrolled cell proliferation, leading to neoplastic cell growth. The Ras/Raf/MEK/ERK signalling pathway is also a complex network of sequentially activated proteins that play a major role in the onset and development of cancer. It can regulate not only the biological functions, such as cell proliferation, cycle regulation, cell differentiation, apoptosis and tissue formation, but it is also associated with tumor development. Stable mutations in the genome or defects in the epigenome lead to dysregulation in the normal biological cycle of the cell, underlying DNA chain damage or dysfunction in the control system, determined by various types of carcinogenic factors, both known and unknown.

Biological Role of CDK 11 and 12 in Cell Cycle and its Function in Tumorigenesis

2020 ◽  
Author(s):  
Shamim Mushtaq
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Web Of Science ◽  
The Body ◽  
Main Role ◽  
Hallmarks Of Cancer ◽  
Cyclin Dependent Kinases ◽  
Tumor Studies ◽  
Cycle Regulation

Uninhibited proliferation and abnormal cell cycle regulation are the hallmarks of cancer. The main role of cyclin dependent kinases is to regulate the cell cycle and cell proliferation. These protein kinases are frequently down regulated or up regulated in various cancers. Two CDK family members, CDK 11 and 12, have contradicting views about their roles in different cancers. For example, one study suggests that the CDK 11 isoforms, p58, inhibits growth of breast cancer whereas, the CDK 11 isoform, p110, is highly expressed in breast tumor. Studies regarding CDK 12 show variation of opinion towards different parts of the body, however there is a consensus that upregulation of cdk12 increases the risk of breast cancer. Hence, CDK 11 and CDK 12 need to be analyzed to confirm their mechanism and their role regarding therapeutics, prognostic value, and ethnicity in cancer. This article gives an outline on both CDKs of information known up to date from Medline, PubMed, Google Scholar and Web of Science search engines, which were explored and thirty relevant researches were finalized.

scholarly journals Polyamine Biosynthetic Pathway as a Drug Target for Osteosarcoma Therapy

2018 ◽  
Vol 6 (3) ◽  
pp. 65 ◽  
Author(s):  
Rebecca Weicht ◽  
Chad Schultz ◽  
Dirk Geerts ◽  
Katie Uhl ◽  
André Bachmann
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Differentiation ◽  
Cell Lines ◽  
High Performance ◽  
Tumor Development ◽  
Oral Drug ◽  
Differentiation Markers ◽  
Cellular Effects ◽  
Medical Advances

Osteosarcoma (OS) is the most common bone tumor in children. Polyamines (PAs) are ubiquitous cations involved in many cell processes including tumor development, invasion and metastasis. In other pediatric cancer models, inhibition of the PA biosynthesis pathway with ornithine decarboxylase (ODC) inhibitor alpha-difluoromethylornithine (DFMO) results in decreased cell proliferation and differentiation. In OS, the PA pathway has not been evaluated. DFMO is an attractive, orally administered drug, is well tolerated, can be given for prolonged periods, and is already used in pediatric patients. Three OS cell lines were used to study the cellular effects of PA inhibition with DFMO: MG-63, U-2 OS and Saos-2. Effects on proliferation were analyzed by cell count, flow cytometry-based cell cycle analysis and RealTime-Glo™ MT Cell Viability assays. Intracellular PA levels were measured with high-performance liquid chromatography (HPLC). Western blot analysis was used to evaluate cell differentiation. DFMO exposure resulted in significantly decreased cell proliferation in all cell lines. After treatment, intracellular spermidine levels were drastically decreased. Cell cycle arrest at G2/M was observed in U-2 OS and Saos-2. Cell differentiation was most prominent in MG-63 and U-2 OS as determined by increases in the terminal differentiation markers osteopontin and collagen 1a1. Cell proliferation continued to be suppressed for several days after removal of DFMO. Based on our findings, DFMO is a promising new adjunct to current osteosarcoma therapy in patients at high risk of relapse, such as those with poor necrosis at resection or those with metastatic or recurrent osteosarcoma. It is a well-tolerated oral drug that is currently in phase II clinical trials in pediatric neuroblastoma patients as a maintenance therapy. The same type of regimen may also improve outcomes in osteosarcoma patients in whom there have been essentially no medical advances in the last 30 years.

scholarly journals Expression of p27Kip1 in Osteoblast-Like Cells during Differentiation with Parathyroid Hormone*

Endocrinology ◽  
1997 ◽  
Vol 138 (5) ◽  
pp. 1995-2004 ◽  
Author(s):  
Takehisa Onishi ◽  
Keith Hruska
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Osteogenic Sarcoma ◽  
S Phase ◽  
G1 Phase ◽  
Osteoblastic Cell ◽  
Cyclin Dependent Kinases ◽  
Kinase A

Abstract PTH is a major systemic regulator of bone metabolism and plays an important role in both bone formation and resorption. PTH either inhibits or stimulates osteoblastic cell proliferation depending on the model that is studied. We analyzed the cell cycle of the UMR-106 cell line, a relatively differentiated osteoblastic osteogenic sarcoma line in which PTH is known to inhibit proliferation but the mechanism of action is unknown. PTH decreased the proportion of cells in S phase and increased the number of G1 phase cells. We examined the effect of PTH on the regulators of the G1 phase cyclin-dependent kinases and found that PTH increased p27Kip1, but not p21Cip1, levels. This effect was mimicked by 8-bromo-cAMP, but not by phorbol 12-myristate 13-acetate. The protein kinase A inhibitor KT5720 abolished the effect of PTH on the increase in p27Kip1 expression. PTH increased CDK2-associated p27Kip1 without affecting the levels of CDK2. CDK2 activity was down-regulated by both PTH and 8-bromo-cAMP treatment. These data suggest that PTH blocks entry of cells into S phase and inhibits cell proliferation as the consequence of an increase in p27Kip1, which is mediated through the protein kinase A pathway. The inhibition of G1 cyclin-dependent kinases by p27Kip1 could cause a reduction of phosphorylation of key substrates and inactivation of transcription factors essential for entry into S phase. The inhibition of cell cycle progression through PKA-mediated p27Kip1 induction might play an important role in PTH-induced differentiation of osteoblasts.

p205, A potential tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation

FEBS Letters ◽  
2006 ◽  
Vol 580 (5) ◽  
pp. 1205-1214 ◽  
Author(s):  
Benyam Asefa ◽  
Jonathan M. Dermott ◽  
Philipp Kaldis ◽  
Karen Stefanisko ◽  
David J. Garfinkel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cell Cycle Regulation ◽  
Cycle Regulation ◽  
Potential Tumor Suppressor

scholarly journals Cell cycle-dependent phosphorylation and regulation of cellular differentiation

2018 ◽  
Vol 46 (5) ◽  
pp. 1083-1091 ◽  
Author(s):  
Laura J.A. Hardwick ◽  
Roberta Azzarelli ◽  
Anna Philpott
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Diverse Range ◽  
Cyclin Dependent Kinases ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Cycle Dependent ◽  
Cell Cycle Dynamics ◽  
Bidirectional Interactions

Embryogenesis requires an exquisite regulation of cell proliferation, cell cycle withdrawal and differentiation into a massively diverse range of cells at the correct time and place. Stem cells also remain to varying extents in different adult tissues, acting in tissue homeostasis and repair. Therefore, regulated proliferation and subsequent differentiation of stem and progenitor cells remains pivotal throughout life. Recent advances have characterised the cell cycle dynamics, epigenetics, transcriptome and proteome accompanying the transition from proliferation to differentiation, revealing multiple bidirectional interactions between the cell cycle machinery and factors driving differentiation. Here, we focus on a direct mechanistic link involving phosphorylation of differentiation-associated transcription factors by cell cycle-associated Cyclin-dependent kinases. We discuss examples from the three embryonic germ layers to illustrate this regulatory mechanism that co-ordinates the balance between cell proliferation and differentiation.

scholarly journals Cell Cycle Regulation of Cyclin-Dependent Kinases in Tobacco Cultivar Bright Yellow-2 Cells

2001 ◽  
Vol 126 (3) ◽  
pp. 1214-1223 ◽  
Author(s):  
David A. Sorrell ◽  
Margit Menges ◽  
J.M. Sandra Healy ◽  
Yves Deveaux ◽  
Chinatsu Amano ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Cyclin Dependent Kinases ◽  
Bright Yellow ◽  
Tobacco Cultivar ◽  
Cycle Regulation

MAGE-C1/CT7 Inhibition Increases Myeloma Cell Line Sensitivity to Bortezomib-Induced Apoptosis: New Target for Myeloma Therapy?

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1908-1908
Author(s):  
Fabricio de Carvalho ◽  
Erico T. Costa ◽  
Anamaria A. Camargo ◽  
Juliana C. Gregorio ◽  
Cibele Masotti ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cell Cycle Regulation ◽  
Myeloma Cell ◽  
Myeloma Cell Line ◽  
Empty Vector ◽  
M Phase ◽  
Induced Apoptosis ◽  
Cycle Regulation

Abstract Abstract 1908 Introduction: MAGE-C1/CT7 encodes for a cancer/testis antigen (CTA) frequently expressed in multiple myeloma (MM) that may be a potential target for immunotherapy in this still incurable disease. The expression of this CTA is restricted to malignant plasma cells and a positive correlation between MAGEC1/CT7 expression and advanced stage has been demonstrated for MM. It has been suggested that MAGE-C1/CT7 might play a pathogenic role in MM; however, the exact function of this protein in the pathophysiology of MM is not yet understood. Objectives: (1) To clarify the role of MAGE-C1/CT7 in the control of cellular proliferation and cell cycle regulation in myeloma cell line SKO-007 and (2) to evaluate the impact of silencing MAGE-C1/CT7 on cells treated with bortezomib. Material and Methods: Short hairpin RNA (shRNA) specific for MAGE-C1/CT7 was inserted in the pRETROSUPER(pRS) retroviral vector. The pRS-shRNA-MAGE-C1/CT7 was co-transfected with pCL-amphotropic packing vector in 293T cells to produce virus particles. Sko-007 myeloma cell line was transduced for stable expression of shRNA-MAGE-C1/CT7. Downregulation of MAGE-C1/CT7 was confirmed by real time PCR (RQ-PCR) and western blot. Functional studies included cell proliferation, cell cycle analysis using propidium iodide, and analysis of apoptosis using annexin V staining. Results: SKO-007 MM cell line was transduced for stable expression of shRNA-MAGE-C1/CT7. SKO-007 cells were divided into three derivatives: empty vector (pRS) and ineffective shRNA (antisense strand deleted – GC bases) [both used as controls for all the experiments] and inhibited (shMAGE-C1/CT7). MAGE-C1/CT7 mRNA expression was ∼5 times lower in inhibited cell line than control cells by RQ-PCR. Western blot showed 70–80% decrease in MAGE-C1/CT7 protein expression in inhibited cells when compared with controls. Functional assays did not indicate a difference in cell proliferation and DNA synthesis when inhibited cells were compared with controls. We used empty vector, ineffective shRNA and inhibited cells to determine whether inhibition of MAGE-C1/CT7 was associated with cell cycle dysregulation. We detected differences between inhibited cells and both controls regarding the proportion of myeloma cells in the G2/M phase (p<0.05). When inhibited cells and controls were treated with 10 nM bortezomib for 48h, inhibited cells showed a 48% reduction of cells in the G2/M phase but control cells have 11% (empty vector) and 10% (ineffective shRNA) of reduction (p<0.05). Inhibited cells treated with 15 nM bortezomib showed an increased percentage of apoptotic cells in comparison with bortezomib treated controls (p<0.01) [Figure]. Conclusions: MAGE-C1/CT7 antigen inhibition did not change cell proliferation and DNA synthesis in SKO-007 cells. However, we found that MAGE-C1/CT7 plays in cell cycle regulation, protecting SKO-007 cells against bortezomib-induced apoptosis. Therefore, MAGE-C1/CT7 silencing by shRNA could be a strategy for future therapies in MM, i.e. in combination with proteasome inhibitors. [Supported by CNPq and LICR] Disclosures: No relevant conflicts of interest to declare.

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