Non-Hodgkin Lymphoma
Tariq I. Mughal in Precision Haematological Cancer Medicine, 2018
Mantle cell lymphoma (MCL) is a molecularly intriguing malignancy in which the t(11;14)(q13;q32) translocation, associated with the cell cycle regulator CCND1 (11q13) and IGH locus (14q32), leads to the constitutive overexpression of cyclin D1. Cyclin D binds to CDK4/6 and causes cell cycle deregulation. It is proposed that this, together with the acquisition of genetic alternations in the BCR and other signalling pathways play a pivotal role in its lymphomagenesis. Two variants, based on the presence or absence of the transcription factor SOX11, and various mutations that affect DNA repair genes (ATM, CCND1 and TP53), epigenetic modifiers (WHSC1, MLL2, MEF2B, RB1, POT1 and SMARCA4A) have been described. Patients with clinically aggressive disease often have activating NOTCH 1/2 and BIRC3 mutations.
The genetics of breast and ovarian cancer
J. K. Cowell in Molecular Genetics of Cancer, 2003
Telomerase activity has been reported in over 90% of breast carcinomas (Landberg et al., 1997). This activity is also associated with cell cycle deregulation, such as up-regulated cyclin D and E levels and increased cell proliferation (Landberg et al., 1997). Similarly, telomerase activity has been reported in almost all malignant ovarian carcinomas, the majority of borderline ovarian tumors and up to 28% of benign ovarian lesions studied, with the intensity of telomerase activity higher in the malignant carcinomas than the other tumor stages (Park et al., 1999). Both TERC (hTR), the gene encoding the telomerase RNA component (Kyo et al., 1999) and TERT, the telomerase catalytic subunit, mRNAs are reported to be up-regulated in benign, borderline and malignant ovarian tumors (Oishi et al., 1998). This may suggest that the altered expression of these genes may also play an important role in the malignant progression of ovarian tumors.
CDK Inhibitors in Leukemia and Lymphoma
Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey in Innovative Leukemia and Lymphoma Therapy, 2019
Aberrations in cell cycle–regulatory molecules in human cancers occur most frequently in molecules associated with control of G1→S transition, a key step that determines initiation of the cell cycle. In fact, dysregulation of cyclin D/CDK4,6/INK4/pRb/E2F signaling pathway has been identified in more than 80% of human cancers (9). In the case of T-cell lymphomas, abnormalities in expression of the endogenous CDK inhibitors p15, p16, and p21 frequently occur (10). Overexpression of cyclin D (primarily cyclin D1) is also common in a variety of human cancers and represents a hallmark of mantle cell lymphoma (11). Aberrant overexpression of cyclin Dl usually stems from gene rearrangement [e.g., of chromosomes 11p15;q13, and t11;14(q13;q32)], gene amplification, or alternative splicing (which generates a cyclin D1b transcript with constitutively nuclear localization and enhanced transforming capacity) (12). Gene amplification and overexpression of cyclins D2 and D3 are also found in some cancers, such as B-cell malignancies including lymphoma. Collectively, these findings strongly support the notion that cell cycle-regulatory CDKs (cyclin D–dependent kinases in particular) represent attractive therapeutic targets in leukemia and lymphoma (13). Figure 1 summarizes the current understanding of cell cycler–elated abnormalities in human leukemia and lymphoma as well as known mechanisms of action of clinically relevant CDK inhibitors.
Wedelolactone suppresses cell proliferation and migration through AKT and AMPK signaling in melanoma
Published in Journal of Dermatological Treatment, 2019
WDL was also able to regulate cell cycle. Peng et al. described that WDL treatment decreased the expression of cyclin D1 while enhanced the expression of p21 (10). Cyclin D was a member of the cyclin protein family which is involved in regulating cell-cycle progression. Cyclin D was required for tumorigenesis as inactivation of cyclin D reduced rumor growth of breast tumor and gastrointestinal tumor (22). In contrast, overexpression of cyclin D induced cell proliferation, increased cell survival and induced mammary tumorgenesis (23). p21 was cyclin-dependent kinase inhibitor which bound to and inhibited the activity of cyclin–CDK complexes. Consistent to previous report, WDL treatment significantly promoted p21 expression in MV3 cells. The decreased expression of cyclin D and increased expression of p21 by WDL treatment indicated that cell cycle was arrested by WDL, which was responsible for the inhibitory effect of WDL on MV3 cells proliferation.
Watercress-based electrospun nanofibrous scaffolds enhance proliferation and stemness preservation of human adipose-derived stem cells
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Mehdi Dadashpour, Younes Pilehvar-Soltanahmadi, Seyed Abolghasem Mohammadi, Nosratollah Zarghami, Mohammad Pourhassan-Moghaddam, Effat Alizadeh, Mohammad Jafar Maleki, Akram Firouzi-Amandi, Mohammad Nouri
Cyclin D is one of the members of the cyclin family that participates in regulating cell cycle progression via triggering cyclin-dependent kinase (Cdk) enzymes [49]. Synthesis of cyclin D1 in the normal cell cycle is initiated during the G1 phase and pushes the G1/S phase transition. Cyclin D-Cdk4/6 complex phosphorylates pRb, causing activation of E2F transcriptional system. Hence, the expression level of cyclin D1 is controlled positively by pRb. Our results support this view that WE-loaded PCL-PEG nanofiber upregulate cyclin D1 expression and subsequently increase the expression of the pRb. But, this phenomenon was not perceived in control, indicating WE-loaded PCL-PEG nanofiber may facilitate the entry of cells into S phase. These observations are further supported by the notable decrease in the quantity of cells in the G0/G1 phase as presented in Table 3. The quantity of cells in the G0/G1 phase of the cell cycle reduced considerably from 84.32 ± 0.006% in PCL-PEG nanofiber to 82.35% ± 0.009% in the WE-loaded PCL-PEG nanofibers (p ≤ .05), suggesting that the presence of WE in electro spun nanofibers may have an influence on accelerating the S phase entry. Moreover, we were interested to study whether the proliferating cells are enduring normal cell proliferation process because uncontrolled cell proliferation has been described as a sign of cancer. Therefore, we compared pRb and p53 gene expression as they are the two most important tumor suppressor genes in cultured cells on WE-loaded PCL-PEG nanofiber and TCP.
Effects of MFG-E8 expression on the biological characteristics of ovarian cancer cells via the AKT/mTOR/S6K signalling pathway
Published in Journal of Obstetrics and Gynaecology, 2023
Na Li, Yazhuo Wang, Lin Liu, Pei Wang, Xiaohua Wu
The G1/S phase transition of the cell cycle is controlled by cyclin-dependent protein kinases. The kinase-cyclin complex, which modulates the kinase activity, regulates cell cycle progression by targeted phosphorylation. The activity of these complexes peaks during the G1/S transition of the cell cycle and promotes cell mitosis (Lee et al.2019). Cyclin D mainly regulates the G1/S cell cycle transition, and its expression is closely related to the abnormal proliferation of tumours (Blain 2008). Besides, MFG-E8 could promote the proliferation of human pulmonary artery smooth muscle cells via p-Akt/cyclin D1 pathway (Wang et al.2021). Our present study showed consistent changes in cell proliferation and expression of cyclin D1 and CDK4 after MFG-E8 silence. Previous studies have focussed on the role of MFG-E8 in artery smooth muscle cells (VSMC) (Wang et al.2012, 2021), however, our study confirmed that MFG-E8 is involved in cell cycle regulation, which could help us better understand the mechanism of MFG-E8 in tumours.
Related Knowledge Centers
- Cullin
- Cyclin
- Cyclin E
- Retinoblastoma Protein
- Amino Acid
- Cell Cycle
- G1/S Transition
- Cyclin-Dependent Kinase
- Anaphase-Promoting Complex
- Cyclin-Dependent Kinase 2