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• W68910239 abstract "As shown in the past potassium ion channels (K+ channels) and chloride ion channels (Cl- channels) are important for proliferation and survival of cancer cells. These ion channels are differentially activated in cancer cells compared to normal tissue or cells.The human colonic cancer cell line T84 was used for in vitro studies on K+ channels and the putative Cl- channel Bestrophin 1 (Best1). The expression of many different K+ channel types was screened by RT-PCR. However, only voltage-gated (Kv) channels have an impact on cell proliferation. Measurements of cell volume, intracellular pH, and intracellular Ca2+ concentration demonstrate that Kv channels control proliferation by affecting intracellular pH and Ca2+ signaling, but not by cell volume regulation.In further cell culture experiments two different clones of T84 cells were generated: a slow proliferating clone (T84- slow) and a fast proliferating clone (T84- fast). Expression of the Kv channel Eag1 and the putative Cl- channel Best1 was enhanced in T84- fast as compared to T84- slow. ATP-induced enhancement of the intracellular Ca2+ concentration was increased in T84- fast, indicating that Kv channels hyperpolarize the cell membrane and therefore enhance the driving force for Ca2+, which is necessary for cell cycle progression. Down regulation of Eag1 or Best1 by RNAi decreased cell proliferation in T84-fast. Furthermore, Best1 over expression in T84-slow increased the proliferation rate by 30% and improved cell volume regulation. These experiments demonstrate that Eag channels and Best1 have an important role in proliferation of colonic cancer cells.For the second part of this study the role of Kv channels in colonic cancer was evaluated in vivo in an animal model. The molecular and functional expression of these ion channels found in vitro in T84 cells were examined first in a chemical mouse model. For this purpose BL6 mice were treated with the chemical carcinogens DMH and MNU to induce the development of colonic cancer and to investigate ion channel properties in early stages of carcinogenesis. In carcinogen treated mice electrogenic salt transport by the epithelial sodium channel ENaC and the chloride channel CFTR were attenuated. In addition, activity of Kv channels was enhanced. Already in the first weeks after treatment semi-quantitative PCR showed an mRNA upregulation of the Kv channels Kv1.3, Kv1.5, Kv3.1, Eag1, Elk1, and Erg1. At the same time an increased Eag1 protein expression could be demonstrated. Furthermore, in cooperation with a group in Basel a genomic amplification of Eag1 was found in 3.5% of human colorectal adenocarcinomas identified by fluorescence in situ hybridization analysis (FISH).A second in vivo study was performed in a genetic mouse model of colonic cancer. BL6 mice with a mutation in the tumor suppressor gene APC (APC-Min/+) develop polyps in the whole intestine. These APC-Min/+ mice showed a significant weight loss and a reduced lifespan during an observation period of 21 weeks. An increased mRNA expression of the Kv channel Eag1, the Ca2+ sensitive Kv channel BK and the sodium channel ENaC could be detected by real time PCR. Ussing chamber studies demonstrated an enhanced sodium absorption by ENaC and an enhanced activity of BK and Eag1 channels.In summary activity of Kv channels like members of Kv1, Eag, or Ca2+ sensitive BK showed a direct correlation to cell proliferation and cancer development in vitro and in vivo. These channels may represent an important target for diagnosis and novel therapeutics of colonic cancer." @default.
• W68910239 created "2016-06-24" @default.
• W68910239 creator A5038033372 @default.
• W68910239 date "2008-02-10" @default.
• W68910239 modified "2023-09-27" @default.
• W68910239 title "Role of potassium ion channels (K+ channels) on proliferation and development of colonic cancer" @default.
• W68910239 cites W12417705 @default.
• W68910239 cites W1485534662 @default.
• W68910239 cites W1510528076 @default.
• W68910239 cites W1536690700 @default.
• W68910239 cites W1568284676 @default.
• W68910239 cites W1598136252 @default.
• W68910239 cites W1611419331 @default.
• W68910239 cites W1718849794 @default.
• W68910239 cites W1807550697 @default.
• W68910239 cites W1870243448 @default.
• W68910239 cites W187520327 @default.
• W68910239 cites W1964124586 @default.
• W68910239 cites W1964754538 @default.
• W68910239 cites W1968623360 @default.
• W68910239 cites W1970120474 @default.
• W68910239 cites W1971697506 @default.
• W68910239 cites W1973225748 @default.
• W68910239 cites W1974302210 @default.
• W68910239 cites W1974626059 @default.
• W68910239 cites W1976128207 @default.
• W68910239 cites W1976194286 @default.
• W68910239 cites W1976492799 @default.
• W68910239 cites W1977528257 @default.
• W68910239 cites W1978057217 @default.
• W68910239 cites W1982877610 @default.
• W68910239 cites W1982991759 @default.
• W68910239 cites W1983719539 @default.
• W68910239 cites W1986872525 @default.
• W68910239 cites W1986937402 @default.
• W68910239 cites W1987652073 @default.
• W68910239 cites W1988449174 @default.
• W68910239 cites W1989318364 @default.
• W68910239 cites W1989970624 @default.
• W68910239 cites W1990606472 @default.
• W68910239 cites W1992469933 @default.
• W68910239 cites W1995073124 @default.
• W68910239 cites W1995819860 @default.
• W68910239 cites W1996423471 @default.
• W68910239 cites W1997727989 @default.
• W68910239 cites W1999073594 @default.
• W68910239 cites W2001258296 @default.
• W68910239 cites W2006305093 @default.
• W68910239 cites W2011404006 @default.
• W68910239 cites W2011782506 @default.
• W68910239 cites W2013306879 @default.
• W68910239 cites W2016281393 @default.
• W68910239 cites W2021244375 @default.
• W68910239 cites W2021392924 @default.
• W68910239 cites W2024450126 @default.
• W68910239 cites W2027803036 @default.
• W68910239 cites W2028335226 @default.
• W68910239 cites W2029179317 @default.
• W68910239 cites W2029489419 @default.
• W68910239 cites W2040153309 @default.
• W68910239 cites W2044643325 @default.
• W68910239 cites W2051292461 @default.
• W68910239 cites W2051357113 @default.
• W68910239 cites W2052870426 @default.
• W68910239 cites W2054567921 @default.
• W68910239 cites W2057830803 @default.
• W68910239 cites W2062608680 @default.
• W68910239 cites W2064414056 @default.
• W68910239 cites W2064821447 @default.
• W68910239 cites W2069898130 @default.
• W68910239 cites W2072880839 @default.
• W68910239 cites W2076298575 @default.
• W68910239 cites W2078784465 @default.
• W68910239 cites W2080804850 @default.
• W68910239 cites W2085385977 @default.
• W68910239 cites W2086544742 @default.
• W68910239 cites W2087810003 @default.
• W68910239 cites W2091065212 @default.
• W68910239 cites W2091531959 @default.
• W68910239 cites W2093531978 @default.
• W68910239 cites W2093960204 @default.
• W68910239 cites W2097664895 @default.
• W68910239 cites W2098162519 @default.
• W68910239 cites W2100270680 @default.
• W68910239 cites W2101179323 @default.
• W68910239 cites W2105703028 @default.
• W68910239 cites W2106253081 @default.
• W68910239 cites W2109974809 @default.
• W68910239 cites W2112815040 @default.
• W68910239 cites W2122872071 @default.
• W68910239 cites W2124271873 @default.
• W68910239 cites W2124608352 @default.
• W68910239 cites W2129737699 @default.
• W68910239 cites W2131118533 @default.
• W68910239 cites W2132349680 @default.
• W68910239 cites W2135271579 @default.
• W68910239 cites W2135426025 @default.
• W68910239 cites W2137135205 @default.
• W68910239 cites W2138377790 @default.
• W68910239 cites W2141412048 @default.

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