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Cell growth

About: Cell growth is a research topic. Over the lifetime, 104237 publications have been published within this topic receiving 3751303 citations. The topic is also known as: GO:0016049 & cellular growth.


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Journal ArticleDOI
TL;DR: The mTOR pathway is activated in a subset of hepatocellular carcinoma and rapamycin can inhibit proliferation of neoplastic hepatocytes in cell culture.
Abstract: Purpose: mTOR and P70 S6 kinase (S6K) play a key role in regulating protein translation. The role of mTOR and S6K in hepatocellular carcinoma has not been investigated, but this pathway is of particular interest because an effective inhibitor, rapamycin, is available. This study was undertaken to determine the prevalence and clinicopathological correlates of mTOR pathway activation in hepatocellular carcinoma and to determine whether rapamycin inhibits the pathway in cell culture. Experimental Design: Total and phosphorylated mTOR and S6K protein expression were studied by immunohistochemistry in hepatocellular carcinomas ( n = 73), fibrolamellar carcinomas ( n = 13), and hepatic adenomas ( n = 15). Results were correlated with tumor growth pattern as defined by the WHO (trabecular, pseudoglandular/acinar, compact, and scirrhous), tumor size, Ki-67 proliferation index, and the modified Edmondson nuclear grade, which has a scale of 1 to 4. HepG2 and Hep3B cell lines were treated with rapamycin to see the effect on proliferation and S6K phosphorylation. Results: Increased expression of total mTOR was seen in 5% of hepatocellular carcinoma, whereas overexpression of phospho-mTOR was evident in 15% of hepatocellular carcinoma. Phospho-mTOR positivity correlated with increased expression of total S6K, which was found in 45% of cases. Total S6K overexpression was positively correlated with tumor nuclear grade, inversely with tumor size, and was unassociated with the proliferation index or WHO growth pattern. Rapamycin treatment of HepG2 and Hep3B cell lines markedly inhibited cell proliferation and reduced S6K phosphorylation in both cell lines. Conclusions: The mTOR pathway is activated in a subset of hepatocellular carcinoma. Rapamycin can inhibit proliferation of neoplastic hepatocytes in cell culture.

362 citations

Journal Article
TL;DR: Flow-cytometric analysis and microscopic observation suggest that the G2-M arrest by genistein is a unique effect among flavonoids.
Abstract: Genistein, an isoflavone, is a specific inhibitor of tyrosine kinase and topoisomerase II. However, its effect on cell growth is unknown. Therefore, we examined the effects of genistein on cell growth and cell cycle progression and compared its effects with other flavonoids. Genistein inhibited in a dose-dependent manner the growth of HGC-27 cells derived from human gastric cancer. Flow-cytometric analysis showed that genistein almost completely arrested the cell cycle progression at G2-M. This effect was reversible when genistein was removed from the culture medium. In contrast, other flavonoids such as flavone, luteolin, and the structurally similar daidzein arrested the cell cycle at G1. Consistent with the flow-cytometric analysis, microscopic observation showed that genistein did not increase the mitotic index, which supposes that genistein may arrest the cell cycle at G2 or early M. These results suggest that the G2-M arrest by genistein is a unique effect among flavonoids.

361 citations

Journal ArticleDOI
TL;DR: It is suggested that HIF-1alpha contributes to the regulation of growth factor-stimulated glucose metabolism even in the absence of hypoxia.
Abstract: Mammalian cells are believed to have a cell-intrinsic ability to increase glucose metabolism in response to hypoxia. Here we show that the ability of hematopoietic cells to up-regulate anaerobic glycolysis in response to hypoxia is dependent on receptor-mediated signal transduction. In the absence of growth factor signaling, hematopoietic cells fail to express hypoxia-inducible transcription factor (Hif-1alpha) mRNA. Growth factor-deprived hematopoietic cells do not engage in glucose-dependent anabolic synthesis and neither express Hif-1alpha mRNA nor require HIF-1alpha protein to regulate cell survival in response to hypoxia. However, HIF-1alpha is adaptive for the survival of growth factor-stimulated cells, as suppression of HIF-1alpha results in death when growing cells are exposed to hypoxia. Growth factor-dependent HIF-1alpha expression reprograms the intracellular fate of glucose, resulting in decreased glucose-dependent anabolic synthesis and increased lactate production, an effect that is enhanced when HIF-1alpha protein is stabilized by hypoxia. Together, these data suggest that HIF-1alpha contributes to the regulation of growth factor-stimulated glucose metabolism even in the absence of hypoxia.

361 citations

Journal ArticleDOI
TL;DR: The findings suggest that the countervailing balance between NO and Ang II may determine the overall cell population within the vessel wall by regulating genetic programs determining cell death as well as cell growth.
Abstract: This study tests the hypothesis that the control of vascular smooth muscle cell (VSMC) apoptosis is regulated by the antagonistic balance between vasoactive substances such as NO and angiotensin II (Ang II). Moreover, it is postulated that the cellular signaling pathways involved in regulating vessel tone are also coupled to the regulation of programmed cell death. Using an in vitro model system, we documented that the addition of NO donor molecules S -nitroso- N -acetylpenicillamine or sodium nitroprusside to VSMC dose-dependently induced apoptosis as documented by DNA laddering and quantified by analysis of cellular chromatin morphology. The mediator role of the guanylate cyclase signaling pathway in NO-induced apoptosis was evidenced by (1) induction of apoptosis by the 8-bromo-cGMP analogue, (2) potentiation of NO-induced apoptosis by cGMP-specific phosphodiesterase inhibition, and (3) the prevention of NO-induced apoptosis by the inhibition of the cGMP-dependent protein kinase Iα. In contrast, Ang II directly antagonized NO donor– and cGMP analogue–induced apoptosis via activation of the type I Ang II receptor. These findings suggest that the countervailing balance between NO and Ang II may determine the overall cell population within the vessel wall by regulating genetic programs determining cell death as well as cell growth.

361 citations

Journal ArticleDOI
TL;DR: In insights into the processing of cell surface proteins by MMPs and the concomitant effects on physiological processes as well as on disease onset and evolution, leads the way to innovative therapeutic approaches for cancer, aswell as degenerative and inflammatory diseases.
Abstract: Matrix metalloproteinases (MMPs) constitute a family of more than 20 endopeptidases. Identification of specific matrix and non-matrix com- ponents as MMP substrates showed that, aside from their initial role as ex- tracellular matrix modifiers, MMPs play significant roles in highly complex processes such as the regulation of cell behavior, cell-cell communication, and tumor progression. Thanks to the comprehensive examination of the expanded MMP action radius, the initial view of proteases acting in the soluble phase has evolved into a kaleidoscope of proteolytic reactions connected to the cell surface. Important classes of cell surface molecules include adhesion molecules, mediators of apoptosis, receptors, chemokines, cytokines, growth factors, pro- teases, intercellular junction proteins, and structural molecules. Proteolysis of cell surface proteins by MMPs may have extremely diverse biological implica- tions, ranging from maturation and activation, to inactivation or degradation of substrates. In this way, modification of membrane-associated proteins by MMP si scrucial for communication between cells and the extracellular milieu, and determines cell fate and the integrity of tissues. Hence, insights into the processing of cell surface proteins by MMPs and the concomitant effects on physiological processes as well as on disease onset and evolution, leads the way to innovative therapeutic approaches for cancer, as well as degenerative and inflammatory diseases.

361 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20233,956
20226,245
20215,196
20206,247
20196,050
20185,767