scholarly journals Carnitine palmitoyltransferase 1A functions to repress FoxO transcription factors to allow cell cycle progression in ovarian cancer

Oncotarget ◽  
2015 ◽  
Vol 7 (4) ◽  
pp. 3832-3846 ◽  
Author(s):  
Huanjie Shao ◽  
Esraa M. Mohamed ◽  
Guoyan G. Xu ◽  
Michael Waters ◽  
Kai Jing ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Transcription Factors ◽  
Cell Cycle Progression ◽  
Carnitine Palmitoyltransferase ◽  
Cycle Progression ◽  
Foxo Transcription Factors

Phosphoinositide 3-kinase and Forkhead, a switch for cell division

2004 ◽  
Vol 32 (2) ◽  
pp. 360-361 ◽  
Author(s):  
L. Martínez-Gac ◽  
B. Álvarez ◽  
Z. García ◽  
M. Marqués ◽  
M. Arrizabalaga ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Division ◽  
Cell Growth ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Downstream Effector ◽  
Cell Cycle Entry ◽  
Foxo Transcription Factors ◽  
Phosphoinositide 3 Kinase

Cell cycle progression is a tightly controlled process. To initiate cell division, mitogens trigger a number of early signals that promote the G0–G1 transition by inducing cell growth and the activation of G1 cyclins. Activation of cyclin E/cdk2 (cyclin-dependent kinase 2) at the end of G1 is then required to trigger DNA synthesis (S phase entry). Among the early signals induced by mitogens, activation of PI3K (phosphoinositide 3-kinase) appears essential to induce cell cycle entry, as it regulates cell growth signalling pathways, which in turn determine the rate of cell cycle progression. Another mechanisms by which PI3K and its downstream effector protein kinase B regulate cell cycle entry is by inactivation of the FOXO (Forkhead Box, subgroup O) transcription factors, which induce expression of quiescence genes such as those encoding p27kip, p130 and cyclin G2. PI3K/FOXO then work as a complementary switch: when PI3K is active, FOXO transcription factors are inactive. The switch is turned on and off at different phases of the cell cycle, thus regulating cell cycle progression.

scholarly journals B Lymphocytes Differentially Use the Rel and Nuclear Factor κB1 (NF-κB1) Transcription Factors to Regulate Cell Cycle Progression and Apoptosis in Quiescent and Mitogen-activated Cells

1998 ◽  
Vol 187 (5) ◽  
pp. 663-674 ◽  
Author(s):  
Raelene J. Grumont ◽  
Ian J. Rourke ◽  
Lorraine A. O'Reilly ◽  
Andreas Strasser ◽  
Kensuke Miyake ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Transcription Factors ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Cycle Progression ◽  
Nuclear Factor ◽  
Cycle Progression ◽  
Regulate Cell Cycle Progression

Rel and nuclear factor (NF)-κB1, two members of the Rel/NF-κB transcription factor family, are essential for mitogen-induced B cell proliferation. Using mice with inactivated Rel or NF-κB1 genes, we show that these transcription factors differentially regulate cell cycle progression and apoptosis in B lymphocytes. Consistent with an increased rate of mature B cell turnover in naive nfkb1−/− mice, the level of apoptosis in cultures of quiescent nfkb1−/−, but not c-rel−/−, B cells is higher. The failure of c-rel−/− or nfkb1−/− B cells to proliferate in response to particular mitogens coincides with a cell cycle block early in G1 and elevated cell death. Expression of a bcl-2 transgene prevents apoptosis in resting and activated c-rel−/− and nfkb1−/− B cells, but does not overcome the block in cell cycle progression, suggesting that the impaired proliferation is not simply a consequence of apoptosis and that Rel/NF-κB proteins regulate cell survival and cell cycle control through independent mechanisms. In contrast to certain B lymphoma cell lines in which mitogen-induced cell death can result from Rel/NF-κB–dependent downregulation of c-myc, expression of c-myc is normal in resting and stimulated c-rel−/− B cells, indicating that target gene(s) regulated by Rel that are important for preventing apoptosis may differ in normal and immortalized B cells. Collectively, these results are the first to demonstrate that in normal B cells, NF-κB1 regulates survival of cells in G0, whereas mitogenic activation induced by distinct stimuli requires different Rel/NF-κB factors to control cell cycle progression and prevent apoptosis.

MiR-17-5p Up-Regulates YES1 to Modulate the Cell Cycle Progression and Apoptosis in Ovarian Cancer Cell Lines

2015 ◽  
Vol 116 (6) ◽  
pp. 1050-1059 ◽  
Author(s):  
Lan Li ◽  
Li He ◽  
Jian-Li Zhao ◽  
Jing Xiao ◽  
Min Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Cycle Progression ◽  
Ovarian Cancer Cell Lines

Evaluation of GPER agonist G-1 combined with navitoclax in platinum-resistant and -sensitive ovarian cancer cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13563-e13563
Author(s):  
Dennis C. DeSimone ◽  
Trung T. Nguyen ◽  
Eugen Brailiou ◽  
John C. Taylor ◽  
Gabriela Cristina Brailoiu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Parp Cleavage ◽  
Ovarian Cancer Cells ◽  
Cycle Progression ◽  
Platinum Based Chemotherapy ◽  
Induced Apoptosis ◽  
In Cells

e13563 Background: Most ovarian cancer patients are treated with platinum-based chemotherapy but eventually relapse with incurable disease. The G protein-coupled estrogen receptor GPER (GPR30) mediates Ca2+ mobilization in response to estrogen and G-1, a synthetic agonist. Large and sustained Ca2+ responses can lead to mitochondrial Ca2+ overload and apoptosis. Hence, we evaluated whether G-1 could induce apoptosis in cisplatin-sensitive A2780 and isogenic cisplatin–resistant CP70 (14-fold resistant), C30 (70-fold resistant) and C200 (157-fold resistant) human ovarian cancer cells. Bcl-2 and Bcl-xL protect mitochondria from Ca2+overload, and were overexpressed in these cisplatin-resistant cells; thus we also examined combining the Bcl-2 family inhibitor navitoclax with G-1. Methods: Cytoplasmic [Ca2+]c and mitochondrial [Ca2+]m were monitored using microscopy and fluorescent Ca2+ probes. Cell cycle, apoptosis and mitochondrial membrane potential (MMP) were assessed by flow cytometry of propidium iodide, Annexin V and DiIC1(5) -stained cells. The intracellular Ca2+ chelator BAPTA was used to block Ca2+mobilization. Results: Expression of the 53kDa GPER but not the 38 kDa isoform progressively increased with increasing cisplatin resistance. G-1 elicited sustained [Ca2+]c rises that correlated with 53 kDa GPER expression, followed by rises in [Ca2+]m. In all cells, 2.5 μM G-1 blocked cell cycle progression at G2/M, inhibited proliferation, and induced apoptosis (A2780 > C30 > CP70 ≥ C200). G-1 induced p53, caspase-3 and PARP cleavage, and MMP loss. BAPTA prevented G-1’s cell cycle and apoptotic effects in cells showing large Ca2+ mobilization responses but did not in cells with small Ca2+responses. Combining navitoclax with G-1 superadditively decreased cell viability and increased apoptosis. Conclusions: G-1 blocked cell cycle progression and induced apoptosis via a Ca2+-dependent pathway in cells expressing high 53 kDa GPER levels, but via a Ca2+-independent pathway in cells with low 53 kDa GPER expression. G-1 also interacted cooperatively with naviticlax. Therefore, G-1 plus navitoclax shows potential for therapeutic use in platinum-sensitive and -resistant ovarian cancer.

scholarly journals The jun and fos protein families are both required for cell cycle progression in fibroblasts.

1991 ◽  
Vol 11 (9) ◽  
pp. 4466-4472 ◽  
Author(s):  
K Kovary ◽  
R Bravo
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Dna Synthesis ◽  
Cell Cycle Progression ◽  
S Phase ◽  
3T3 Cells ◽  
Cycle Progression ◽  
Serum Stimulation ◽  
Fos Protein ◽  
Stimulation Of

The expression of different members of the Jun and Fos families of transcription factors is rapidly induced following serum stimulation of quiescent fibroblasts. To determine whether these proteins are required for cell cycle progression, we microinjected affinity-purified antibodies directed against c-Fos, FosB, Fra-1, c-Jun, JunB, and JunD, and antibodies that recognize either the Fos or the Jun family of proteins, into Swiss 3T3 cells and determined their effects in cell cycle progression by monitoring DNA synthesis. We found that microinjection of anti-Fos and anti-Jun family antibodies efficiently blocked the entrance to the S phase of serum-stimulated or asynchronously growing cells. However, the antibodies against single members of the Fos family only partially inhibited DNA synthesis. In contrast, all three Jun antibodies prevented DNA synthesis more effectively than did any of the anti-Fos antibodies.

TLE Corepressors as Novel Candidate AML Tumor Suppressor Genes That Regulate Wnt Signaling, Cell Cycle Progression, and Myeloid Differentiation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1601-1601
Author(s):  
Farshid Dayyani ◽  
Yuntian Zhang ◽  
Sayyed T. Zaidi ◽  
David A. Sweetser
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Wnt Signaling ◽  
Tumor Suppressor Genes ◽  
Cell Cycle Progression ◽  
Myeloid Cell ◽  
Myeloid Differentiation ◽  
Cd11b Expression ◽  
Cycle Progression ◽  
Over Expression

Abstract Deletion of the long arm of chromosome 9, del(9q), is one of the most common mutations associated with t(8;21) AML. Up to 50% of del(9q) AML is seen in association with t(8;21). The Runx1-ETO (AML1-ETO) fusion gene produced by t(8;21) is insufficient for leukemogenesis and loss of a critical gene(s) on chr9q apparently cooperates in leukemogenesis. We recently identified two members of the Groucho family of co-repressors, Transducin-like enhancer of split (TLE) 1 and TLE4, as candidate tumor suppressor genes, based on our mapping of the commonly deleted region in del(9q) AML. These proteins are known to inhibit Wnt signaling which has been implicated in hematopoietic stem cell renewal and they interact with hematopoietic transcription factors such as Runx1 and Pu.1. We have demonstrated that the expression of these two genes is specifically repressed in both del(9q) and t(8;21) AML samples. Knockdown of TLE1 or TLE4 mRNA using specific small interfering RNAs (siRNA) activates Wnt signaling in 293T cells as measured by TOPFLASH activity, while forced expression of TLE1 or 4 inhibits TOPFLASH. We show that siRNA against TLE4 using a specific siRNA increased cell cycle progression and cell division, while over-expression of TLE1 or TLE4 slowed cell cycle progression and lead to a pronounced growth disadvantage in THP-1 and HL60 myeloid cell lines. In addition to these effects on cell proliferation, these genes also affected myeloid cell differentiation. Over-expression of either TLE1 or TLE4 in monocytic THP-1 and promyelocytic HL-60 cell lines initiated myeloid differentiation as monitored by CD11b expression. These two genes have different effects on more terminal myeloid differentiation as TLE4, but not TLE1, was able to induce more terminal differentiation of THP-1 cells into monocytes as measured by CD14 expression, while TLE1 was able to induce the granulocytic marker CD15 in HL-60 cells. Furthermore, lentiviral delivery of siRNAs for either TLE1 or TLE4 to HL-60 cells inhibited induction of granulocytic and monocytic differentiation with all-trans retinoic acid (ATRA) or 1,25-dihydroxycholechalciferol (Vit.D3). TLE1 siRNA inhibited ATRA and Vit.D3 induced CD11b expression by more than 75%. While TLE4 siRNA decreased the induction of monocytic CD14 after Vit.D3 by 40%, TLE1 siRNA almost completely abrogated induction of CD14 with Vit.D3 or granulocytic CD15 with ATRA in HL-60 cells. Ex vivo culture of siRNA infected CD34 sorted human cord blood (CB) cells in semi-liquid media with differentiation inducing cytokines for seven days exhibited a decrease in the percentage of early CD33+ myeloid cells by 15% and 70% relative to controls in TLE1 and TLE4 siRNA infected CB cells, respectively. These results indicate that inhibition of TLE activity can promote cell cycle progression and inhibit myeloid differentiation. This study is the first to demonstrate a potential role for the TLEs in leukemogenesis and also indicates the TLEs may have non-redundant functions in myeloid differentiation. Understanding how various mutations work cooperatively to produce a malignant phenotype is one of the great challenges in oncology. The TLEs may represent an important cooperating mutation with Runx1-ETO in AML that links Wnt signaling and core binding protein transcription factors. Studies are currently underway to demonstrate this cooperativity.

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