PubMed:15913739 JSONTXT

{"project":"AnEM_abstracts","denotations":[{"id":"T1","span":{"begin":16,"end":20},"obj":"Cell"},{"id":"T2","span":{"begin":64,"end":69},"obj":"Cell"},{"id":"T3","span":{"begin":130,"end":153},"obj":"Cell"},{"id":"T4","span":{"begin":249,"end":253},"obj":"Cell"},{"id":"T5","span":{"begin":300,"end":304},"obj":"Cell"},{"id":"T6","span":{"begin":377,"end":405},"obj":"Cell"},{"id":"T7","span":{"begin":521,"end":541},"obj":"Cell"},{"id":"T8","span":{"begin":585,"end":610},"obj":"Cell"},{"id":"T9","span":{"begin":687,"end":719},"obj":"Cell"},{"id":"T10","span":{"begin":849,"end":853},"obj":"Cell"},{"id":"T11","span":{"begin":975,"end":990},"obj":"Cell"},{"id":"T12","span":{"begin":1007,"end":1043},"obj":"Cell"},{"id":"T13","span":{"begin":1136,"end":1184},"obj":"Cell"},{"id":"T14","span":{"begin":1240,"end":1251},"obj":"Cell"},{"id":"T15","span":{"begin":1310,"end":1314},"obj":"Cell"},{"id":"T16","span":{"begin":1409,"end":1441},"obj":"Cell"},{"id":"T17","span":{"begin":1601,"end":1621},"obj":"Cell"},{"id":"T18","span":{"begin":1636,"end":1640},"obj":"Cell"},{"id":"T19","span":{"begin":1376,"end":1381},"obj":"Cell"},{"id":"T20","span":{"begin":1688,"end":1693},"obj":"Cell"}],"text":"Bcl-2 decreases cell proliferation and promotes accumulation of cells in S phase without affecting the rate of apoptosis in human ovarian carcinoma cells.\nOBJECTIVES: The Bcl-2 protein is an important regulator of the apoptotic cascade and promotes cell survival. Bcl-2 can also delay entry into the cell cycle from quiescence. In the present study, we used two isogenic human ovarian carcinoma cell lines, which expressed differential levels of Bcl-2 proteins, to demonstrate that Bcl-2 may regulate the growth rates of adenocarcinoma cells.\nMETHODS: The growth rates of two isogenic ovarian cancer cell lines were determined by XTT assays and flow cytometry combined with PI staining. Bcl-2-overexpressing SKOV3 cells were modified to express a doxycycline-inducible anti-Bcl-2 single-chain antibody and the effects of Bcl-2 protein inhibition on cell proliferation and apoptosis were assessed.\nRESULTS: We demonstrate that Bcl-2 promotes the accumulation of proliferating carcinoma cells in S phase. The Bcl-2-overexpressing SKOV3 cell line proliferates markedly faster and shows delayed progression to G2M phase compared to its low Bcl-2-expressing counterpart SKOV3.ip1 cell line. Single-chain antibody-mediated inhibition of Bcl-2 in SKOV3 cells was associated with increased growth rates and more rapid cell cycle progression. Treatment with cisplatin resulted in more cells accumulating in S phase in Bcl-2-overexpressing SKOV3 cells, while the inhibition of Bcl-2 abolished delayed entry into G2M phase without affecting cisplatin-induced apoptosis.\nCONCLUSIONS: Our results suggest that, in ovarian cancer cells, Bcl-2 delays cell cycle progression by promoting accumulation of cells in S phase without affecting the rate of apoptosis. Thus, in addition to its known role at the G0/G1 checkpoint, we demonstrate for the first time that Bcl-2 also regulates the S phase."}

{"project":"CoMAGC","denotations":[{"id":"T1","span":{"begin":1467,"end":1472},"obj":"Gene"},{"id":"E2","span":{"begin":1453,"end":1463},"obj":"Negative_regulation"},{"id":"T2","span":{"begin":1430,"end":1435},"obj":"ovarian cancer"}],"relations":[{"id":"R1","pred":"themeOf","subj":"T1","obj":"E2"},{"id":"R3","pred":"CGE-decreased","subj":"T1","obj":"T2"},{"id":"R4","pred":"CCS-normalTOcancer","subj":"T1","obj":"T2"},{"id":"R5","pred":"PT-causality","subj":"T1","obj":"T2"},{"id":"R3","pred":"IGE-unidentifiable","subj":"T1","obj":"T2"}],"text":"Bcl-2 decreases cell proliferation and promotes accumulation of cells in S phase without affecting the rate of apoptosis in human ovarian carcinoma cells.\nOBJECTIVES: The Bcl-2 protein is an important regulator of the apoptotic cascade and promotes cell survival. Bcl-2 can also delay entry into the cell cycle from quiescence. In the present study, we used two isogenic human ovarian carcinoma cell lines, which expressed differential levels of Bcl-2 proteins, to demonstrate that Bcl-2 may regulate the growth rates of adenocarcinoma cells.\nMETHODS: The growth rates of two isogenic ovarian cancer cell lines were determined by XTT assays and flow cytometry combined with PI staining. Bcl-2-overexpressing SKOV3 cells were modified to express a doxycycline-inducible anti-Bcl-2 single-chain antibody and the effects of Bcl-2 protein inhibition on cell proliferation and apoptosis were assessed.\nRESULTS: We demonstrate that Bcl-2 promotes the accumulation of proliferating carcinoma cells in S phase. The Bcl-2-overexpressing SKOV3 cell line proliferates markedly faster and shows delayed progression to G2M phase compared to its low Bcl-2-expressing counterpart SKOV3.ip1 cell line. Single-chain antibody-mediated inhibition of Bcl-2 in SKOV3 cells was associated with increased growth rates and more rapid cell cycle progression. Treatment with cisplatin resulted in more cells accumulating in S phase in Bcl-2-overexpressing SKOV3 cells, while the inhibition of Bcl-2 abolished delayed entry into G2M phase without affecting cisplatin-induced apoptosis.\nCONCLUSIONS: Our results suggest that, in ovarian cancer cells, Bcl-2 delays cell cycle progression by promoting accumulation of cells in S phase without affecting the rate of apoptosis. Thus, in addition to its known role at the G0/G1 checkpoint, we demonstrate for the first time that Bcl-2 also regulates the S phase."}