scholarly journals FGF9/FGFR2 increase cell proliferation by activating ERK 1/2, Rb/E2F1, and cell cycle pathways in mouse Leydig tumor cells

2018 ◽  
Vol 109 (11) ◽  
pp. 3503-3518 ◽  
Author(s):  
Ming‐Min Chang ◽  
Meng‐Shao Lai ◽  
Siou‐Ying Hong ◽  
Bo‐Syong Pan ◽  
Hsin Huang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Cells ◽  
Leydig Tumor Cells

scholarly journals Tumor quiescence: elevating SOX2 in diverse tumor cell types downregulates a broad spectrum of the cell cycle machinery and inhibits tumor growth

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ethan P. Metz ◽  
Erin L. Wuebben ◽  
Phillip J. Wilder ◽  
Jesse L. Cox ◽  
Kaustubh Datta ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Cell Cycle Machinery

Abstract Background Quiescent tumor cells pose a major clinical challenge due to their ability to resist conventional chemotherapies and to drive tumor recurrence. Understanding the molecular mechanisms that promote quiescence of tumor cells could help identify therapies to eliminate these cells. Significantly, recent studies have determined that the function of SOX2 in cancer cells is highly dose dependent. Specifically, SOX2 levels in tumor cells are optimized to promote tumor growth: knocking down or elevating SOX2 inhibits proliferation. Furthermore, recent studies have shown that quiescent tumor cells express higher levels of SOX2 compared to adjacent proliferating cells. Currently, the mechanisms through which elevated levels of SOX2 restrict tumor cell proliferation have not been characterized. Methods To understand how elevated levels of SOX2 restrict the proliferation of tumor cells, we engineered diverse types of tumor cells for inducible overexpression of SOX2. Using these cells, we examined the effects of elevating SOX2 on their proliferation, both in vitro and in vivo. In addition, we examined how elevating SOX2 influences their expression of cyclins, cyclin-dependent kinases (CDKs), and p27Kip1. Results Elevating SOX2 in diverse tumor cell types led to growth inhibition in vitro. Significantly, elevating SOX2 in vivo in pancreatic ductal adenocarcinoma, medulloblastoma, and prostate cancer cells induced a reversible state of tumor growth arrest. In all three tumor types, elevation of SOX2 in vivo quickly halted tumor growth. Remarkably, tumor growth resumed rapidly when SOX2 returned to endogenous levels. We also determined that elevation of SOX2 in six tumor cell lines decreased the levels of cyclins and CDKs that control each phase of the cell cycle, while upregulating p27Kip1. Conclusions Our findings indicate that elevating SOX2 above endogenous levels in a diverse set of tumor cell types leads to growth inhibition both in vitro and in vivo. Moreover, our findings indicate that SOX2 can function as a master regulator by controlling the expression of a broad spectrum of cell cycle machinery. Importantly, our SOX2-inducible tumor studies provide a novel model system for investigating the molecular mechanisms by which elevated levels of SOX2 restrict cell proliferation and tumor growth.

scholarly journals SDF-1α/MicroRNA-134 Axis Regulates Nonfunctioning Pituitary Neuroendocrine Tumor Growth via Targeting VEGFA

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyu Wang ◽  
Yuanjian Fang ◽  
Yunxiang Zhou ◽  
Xiaoming Guo ◽  
Ke Xu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Neuroendocrine Tumor ◽  
Tumor Cells ◽  
Tumor Invasion ◽  
Expression Level ◽  
Qrt Pcr ◽  
Proliferation And Invasion

BackgroundNonfunctioning pituitary neuroendocrine tumor (NF-PitNET) is difficult to resect. Except for surgery, there is no effective treatment for NF-PitNET. MicroRNA-134 (miR-134) has been reported to inhibit proliferation and invasion ability of tumor cells. Herein, the mechanism underlying the effect of miR-134 on alleviating NF-PitNET tumor cells growth is explored.MethodsMouse pituitary αT3-1 cells were transfected with miR-134 mimics and inhibitor, followed by treatment with stromal cell-derived factor-1α (SDF-1α) in vitro. MiR-134 expression level: we used quantitative real-time PCR (qRT-PCR) to detect the expression of miR-134. Cell behavior level: cell viability and invasion ability were assessed using a cell counting kit-8 (CCK8) assay and Transwell invasion assay respectively. Cytomolecular level: tumor cell proliferation was evaluated by Ki-67 staining; propidium iodide (PI) staining analyzed the effect of miR-134 on cell cycle arrest; western blot analysis and immunofluorescence staining evaluated tumor migration and invasive ability. Additionally, we collected 27 NF-PitNET tumor specimens and related clinical data. The specimens were subjected to qRT-PCR to obtain the relative miR-134 expression level of each specimen; linear regression analysis was used to analyze the miR-134 expression level in tumor specimens and the age of the NF-PitNET population, gender, tumor invasion, prognosis, and other indicators.ResultsIn vitro experiment, miR-134 was observed to significantly inhibit αT3-1 cells proliferation characterized by inhibited cell viability and expressions of vascular endothelial growth factor A (VEGFA) and cell cycle transition from G1 to S phase (P < 0.01). VEGFA was verified as a target of miR-134. Additionally, miR-134-induced inhibition of αT3-1 cell proliferation and invasion was attenuated by SDF-1α and VEGFA overexpression (P < 0.01). In primary NF-PitNET tumor analysis, miR-134 expression level was negatively correlated with tumor invasion (P = 0.003).ConclusionThe regulation of the SDF-1α/miR-134/VEGFA axis represents a novel mechanism in the pathogenesis of NF-PitNETs and may serve as a potential therapeutic target for the treatment of NF-PitNETs.

scholarly journals Hydroxyphenyl Butanone Induces Cell Cycle Arrest through Inhibition of GSK3β in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Songyan Zhang ◽  
Yunfeng Wang ◽  
Haopeng Zhang ◽  
Chengming Sun ◽  
Shuwei Dang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Epithelial Cells ◽  
Tumor Cells ◽  
Colony Formation ◽  
Colorectal Cancer Cell Line ◽  
Colonic Epithelial Cells ◽  
Low Concentration ◽  
Key Factor

Background. Colorectal cancer (CRC) is among the top three gastrointestinal malignancy in morbidity and mortality. The abnormal activation of Wnt/β-catenin pathway is considered to be a key factor in the occurrence and development of CRC. Novel inhibitor discovery against key factor in WNT pathway is important for CRC treatment and prevention. Methods. Cell proliferation was detected after hydroxyphenyl butanone treatment in human colorectal cancer HCT116, LOVO, and normal colonic epithelial NCM460 cells. Colony formation, cell invasion ability, and cell cycle were detected with and without GSK-3β knockdown. Results. Hydroxyphenyl butanone induces cycle arresting on G1-S phase of colorectal cancer cell line through GSK3β in Wnt/β-catenin pathway and inhibits malignant biological manifestations of cell proliferation, colony formation, and invasion. The inhibition in the high concentration group is stronger than that in the low concentration group, and the antitumor effect is different for different tumor cells. Under the same concentration of natural hydroxyphenyl butanone, the inhibition on normal colonic epithelial cells is significantly lower than that on tumor cells. The natural hydroxyphenyl butanone with medium and low concentration could promote the proliferation of normal colonic epithelial cells. Conclusion. This study illustrated natural hydroxyphenyl butanone as new inhibitor of GSK3β and revealed the mechanisms underlying the inhibitory effects in colorectal cancer.

Comparative effects of indomethacin on cell proliferation and cell cycle progression in tumor cells grown in vitro and in vivo

2001 ◽  
Vol 61 (5) ◽  
pp. 565-571 ◽  
Author(s):  
Yaniv Eli ◽  
Fiorenza Przedecki ◽  
Galit Levin ◽  
Na’am Kariv ◽  
Amiram Raz
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Cells ◽  
Cell Cycle Progression ◽  
Cycle Progression

Genomic components of carcinogenesis

1993 ◽  
Vol 39 (11) ◽  
pp. 2375-2385 ◽  
Author(s):  
R Schmandt ◽  
G B Mills
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Death ◽  
Growth Factors ◽  
Cell Division ◽  
Programmed Cell Death ◽  
Tumor Cells ◽  
Tumor Suppressor Genes ◽  
Normal Cells ◽  
Biochemical Pathways

Abstract Many of the genes encoding growth factors, growth factor receptors, enzymes, and other effector molecules that regulate normal cell growth are designated protooncogenes. Oncogenes, those genes associated with cellular transformation, differ from their protooncogenic progenitors by being mutated, overexpressed, or expressed at inappropriate times or locations in the cell. One of the activities of growth factors is to prime cells to undergo programmed cell death, which is characterized by a series of morphologic changes called apoptosis. In normal cells, specific mediators must be activated or suppressed to bypass programmed cell death. In tumor cells, either the pathways leading to apoptosis are not functional or the mediators that normally "rescue" cells from this fate are overexpressed or constitutively activated. In addition to the biochemical pathways that drive cell division, there are others that limit cell proliferation; these, designated tumor suppressors, anti-oncogenes, or recessive oncogenes, must be inactivated in normal cells to allow passage through the cell cycle and cell proliferation. In contrast to oncogenes, which are overexpressed or activated in tumors, tumor-suppressor genes are frequently inactivated in tumor cells, either by mutation or deletion. Thus, in normal cells a series of checks and balances must be overcome to allow initiation and continuation of cell division. In tumors, these processes are aberrant, resulting in increased rates of cell division, increases in the proportion of cells in the cell cycle, or increased survival of activated cells. Therefore, tumor cells frequently accumulate genomic alterations, which may result in the activation of a particular array of oncogenes, the inactivation of specific tumor-suppressor genes, and the bypassing of programmed cell death. Trials of antitumor agents that act by exploiting the overexpression of oncogenes in tumors and of the biochemical pathways by which they mediate cell proliferation are currently underway.

TRAIL targets cell cycle arrested tumor cells

2012 ◽  
Vol 224 (03) ◽  
Author(s):  
F Wachter ◽  
M Grunert ◽  
I Jeremias ◽  
H Ehrhardt
Keyword(s):  
Cell Cycle ◽  
Tumor Cells
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