China
Africa
Explore chapters and articles related to this topic
Regulation of Airway Smooth Muscle Proliferation by β2-Adrenoceptor Agonists
Published in Alastair G. Stewart, AIRWAY WALL REMODELLING in ASTHMA, 2020
Alastair G. Stewart, Paul R. Tomlinson, Leslie Schachte
In cell lines that have been constructed to overexpress cyclin D156 or cyclin E,157 the duration of G1 is reduced, the cells are smaller, and there is a diminished requirement for mitogens, indicating the importance of these two cyclins. Microinjection of antibodies against cyclin D1 into fibroblasts overexpressing cyclin D prevented these cells from entering S phase, but these antibodies had no effect when injected near G1/S phase transition.156,158 Cyclin D localises to the nucleus during G1 and disappears from the nucleus as cells proceed into S phase.158 Paradoxically, the acute overexpression of cyclin D1 caused by the microinjection of an expression plasmid into fibroblasts has been shown to prevent entry into S phase.159 This effect may be due to the inhibition of DNA repair in the presence of high levels of cyclin D, which provides an explanation of the difficulty in establishing cell lines with high levels of expression of cyclin D.156
Familial Hyperparathyroidism
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Luigia Cinque, Alfredo Scillitani, Vito Guarnieri
Parafibromin is also implicated in embryonic development directly regulating genes of cell growth and survival, such as the H19 gene, insulin-like growth factors 1 and 2 (IGF1 and IGF2), insulin-like growth factor binding protein 4 (IGFBP4), high mobility AT-hook 1 and 2 (HMGA1 and HMGA2), and 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 (HMGCS2) [85]. Parafibromin was shown to have a dual role as a tumor suppressor and oncoprotein depending on the cellular environment. As a tumor suppressor, parafibromin overexpression seems to result in (i) inhibition of NIH3T3 and HEK293 cell proliferation; (ii) increase in G1 arrest and (iii) apoptosis in Hela cells, and (iv) downregulation of the cell cycle regulator cyclin D1.
CDK Inhibitors in Leukemia and Lymphoma
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Cyclin D1 is a multifunctional protein that plays a critical role not only as a partner of CDK4/6 (see above) in the regulation of the cell cycle (e.g., the G1/S transition) but also as a transcriptional regulator by modulating the activity of several transcriptional factors (e.g., STAT3) that are CDK-independent. This may explain why cyclin D1 is not only involved in cell cycle progression but also in cell growth and survival (25). Cyclin D1 binds to transcriptional factors STAT3 and NeuroD and inhibits their transcriptional activity, which may be related to the modulation of cell differentiation. Cyclin D1 also interacts with histone deacetylases and, in so doing, blocks access of transcriptional factors to the promoter and inhibits loading of initiation complex (26). Cyclin D1, as an oncogene, also plays an important role in carcinogenesis, probably by driving cells into the S phase and cooperating with various oncogenes (such as Myc and Ras) in malignant transformation. Rearrangement of the cyclin D1 locus and/or overexpression of cyclin D1 have been reported in many human tumors, particularly mantle cell lymphoma (27).
circYap inhibits oral squamous cell carcinoma by arresting cell cycle
Published in Acta Odontologica Scandinavica, 2022
Xiao-Yun Zhang, Huifang Tang, Yanping Liu, Nan Du, Songbo Tian, Yong-Qing Dou
Cyclin D1 promotes progression through the G1 phase of the cell cycle. Over expression of cyclin D1 has been reported in various tumours like oesophageal carcinoma, hepatocellular carcinoma, lung carcinoma, and head and neck carcinoma. It is reported that cyclin D1 protein expression is significantly altered from epithelial dysplasia to oral squamous cell carcinomas [23]. CDK4 is one of the main players in cell cycle. Progression from G1 phase to S phase of the mammalian cell cycle is controlled by Cyclin D1 in conjunction with their catalytic partners CDK4 [24]. Cyclin D1/CDK4 complexes form in cytoplasm and are then translocated to the nucleus to promote G1/S transition and are responsible for inactivation of Rb proteins [25]. We predicted whether circYap could bind to Cyclin D1 or CDK4 by RPIseq. The scores indicate circYap may interact with Cyclin D1 and CDK4, respectively. We hypothesized that circYap may bind CDK4 and Cyclin D1 to influence the cell cycle. Next, we used RIP and RNA pull-down assays to confirm the above conjecture. We found that circYap could only bind to CDK4, but could not bind to Cyclin D1. Further experiments showed that overexpression of circYap significantly reduced the interaction between CDK4 and Cyclin D1. Therefore, we demonstrated that circYap may bind CDK4, thereby inhibiting the formation of Cyclin D1 and CDK4 complex, resulting in the retention of Cyclin D1 in the cytoplasm, and leading to cell cycle arrest. Thus, we clarify the mechanism that Cyclin D1 involves in OSCC from another aspect.
Preclinical discovery and development of abemaciclib used to treat breast cancer
Published in Expert Opinion on Drug Discovery, 2021
Matthew D. Wright, Jame Abraham
Increased expression of cyclin D1 occurs in many cancers, including breast, prostate, head and neck, melanoma, and mantle cell lymphoma [19,20]. Both HER2 and ER promote increased cyclin D in breast cancer [17,21]. Preclinical studies revealed that ER-induced growth requires cyclin D, which is a stimulus for CDK4 and CKD6 [22,23]. Cyclin D1 can bind to ER directly causing increased ER-mediated signaling [24]. Antiestrogens, which inhibit growth in ER-positive breast cancers, are associated with decreased expression of cyclin D1 [25]. Resistance to endocrine therapy (ET) in ER-positive breast cancer is accompanied with continual expression of cyclin D1 and Rb phosphorylation [26]. Results from a cancer genome study revealed CDK4/6-cyclin D1 hyper-activation to be common in ER-positive breast cancer [27].
Chemopreventive effect of α-hederin/carboplatin combination against experimental colon hyperplasia and impact on JNK signaling
Published in Toxicology Mechanisms and Methods, 2021
Hoda I. Bahr, Afaf T. Ibrahiem, Attia M. Gabr, Alaaeldeen M. Elbahaie, Hoda S. Elmahdi, Nema Soliman, Amal M. Youssef, Mohamed El-Sherbiny, Sawsan A. Zaitone
The signaling of phosphatidylinositol 3-kinase (PI3K)/AKT/c-Jun N terminal kinase (JNK) pathway is integrated in cell growth, invasion, migration, apoptosis, and cancer regulation (Arcaro and Guerreiro 2007; Kang et al. 2013). AKT is a serine/threonine-specific protein kinase that can consolidate carcinogenesis through Myc and cyclin D1 stabilization (Los et al. 2009). Cyclin D1 is an oncogene that regulates the cell cycle via progression from G1 to S phases and overexpressed in various cancers including colorectal cancer and was correlated with poor prognosis (Ogino et al. 2009; Li et al. 2014). JNK is one of the downstream pathways of PI3K/AKT signaling and offers a pivotal role in apoptotic death and tumorigenesis in a stimulus-dependent mode (Arcaro and Guerreiro 2007; Zhao et al. 2015).