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.
  OBJECTIVES:
  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.
  METHODS:
  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.
  RESULTS:
  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.
  CONCLUSIONS:
  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.
  
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entities.entity_id: PMID-15913739_T1
entities.text: ['cells']
entities.type: Cell
entities.entity_id: PMID-15913739_T2
entities.text: ['ovarian carcinoma cells']
entities.type: Cell
entities.entity_id: PMID-15913739_T3
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entities.type: Cell
entities.entity_id: PMID-15913739_T4
entities.text: ['cell']
entities.type: Cell
entities.entity_id: PMID-15913739_T5
entities.text: ['ovarian carcinoma cell lines']
entities.type: Cell
entities.entity_id: PMID-15913739_T6
entities.text: ['adenocarcinoma cells']
entities.type: Cell
entities.entity_id: PMID-15913739_T7
entities.text: ['ovarian cancer cell lines']
entities.type: Cell
entities.entity_id: PMID-15913739_T8
entities.text: ['Bcl-2-overexpressing SKOV3 cells']
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entities.entity_id: PMID-15913739_T9
entities.text: ['cell']
entities.type: Cell
entities.entity_id: PMID-15913739_T10
entities.text: ['carcinoma cells']
entities.type: Cell
entities.entity_id: PMID-15913739_T11
entities.text: ['Bcl-2-overexpressing SKOV3 cell line']
entities.type: Cell
entities.entity_id: PMID-15913739_T12
entities.text: ['Bcl-2-expressing counterpart SKOV3.ip1 cell line']
entities.type: Cell
entities.entity_id: PMID-15913739_T13
entities.text: ['SKOV3 cells']
entities.type: Cell
entities.entity_id: PMID-15913739_T14
entities.text: ['cell']
entities.type: Cell
entities.entity_id: PMID-15913739_T15
entities.text: ['Bcl-2-overexpressing SKOV3 cells']
entities.type: Cell
entities.entity_id: PMID-15913739_T16
entities.text: ['ovarian cancer cells']
entities.type: Cell
entities.entity_id: PMID-15913739_T17
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entities.entity_id: PMID-15913739_T18
entities.text: ['cells']
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entities.entity_id: PMID-15913739_T19
entities.text: ['cells']
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entities.entity_id: PMID-15913739_T20