Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: Independent prognostic role of p53 and bcl-2

Buglioni, Simonetta; D’Agnano, Igea; Cosimelli, Maurizio; Vasselli, Stefania; D’Angelo, Carmen; Tedesco, Manfredo; Zupi, Gabriella; Mottolese, Marcella

doi:10.1002/(sici)1097-0215(19991222)84:6<545::aid-ijc1>3.0.co;2-2

Cited by 93 publications

(77 citation statements)

References 15 publications

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“…Bcl-2 is expressed in multiple human tumor cell types, including colorectal cancers in the absence of gene rearrangements (47)(48)(49). Because human cancer cells are type II and most chemotherapeutic drugs mediate apoptosis by inducing mitochondrial dysfunction, Bcl-2 is an important contributor to multiple drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis Is Inhibited by Bcl-2 but Restored by the Small Molecule Bcl-2 Inhibitor, HA 14-1, in Human Colon Cancer Cells

Sinicrope

Penington

Tang

2004

Clinical Cancer Research

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Purpose: Tumor necrosis factor-related apoptosisinducing ligand (TRAIL) is a promising anticancer agent that induces apoptosis in multiple tumor cell types while sparing most normal cells. We determined the effect of ectopic Bcl-2 expression on TRAIL-induced apoptosis and whether the small molecule Bcl-2 inhibitor, HA14-1, could increase TRAIL sensitivity. Conclusions: Bcl-2 confers apoptosis resistance to TRAIL by inhibiting a mitochondrial amplification step and by inactivating downstream XIAP in SW480 cells. HA14-1 reversed Bcl-2-mediated TRAIL resistance, suggesting a novel strategy for increasing TRAIL sensitivity in Bcl-2-overexpressing colon cancers.

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Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis Is Inhibited by Bcl-2 but Restored by the Small Molecule Bcl-2 Inhibitor, HA 14-1, in Human Colon Cancer Cells

Sinicrope

Penington

Tang

2004

Clinical Cancer Research

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“…6 In human colon cancer, multiple studies showed that BCL2 expression is correlated with favorable outcome. 27 In multi-stage liver carcinogenesis models, BCL2 expression inhibits the growth of early proliferative foci and counteracts hepatic carcinogenesis induced by TGFa and Myc. 28,29 In support of this, induction of BCL2 also delays hepatocyte cell cycle entry in liver regeneration.…”

Section: Bcl2 Cell Cycle Control and Tumorigenesismentioning

confidence: 99%

BCL2 family in DNA damage and cell cycle control

2006

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Individual BCL2 family members couple apoptosis regulation and cell cycle control in unique ways. Antiapoptotic BCL2 and BCL-x L are antiproliferative by facilitating G0. BAX is proapoptotic and accelerates S-phase progression. The dual functions in apoptosis and cell cycle are coordinately regulated by the multi-domain BCL2 family members (MCL-1) and suggest that survival is maintained at the expense of proliferation. The role of BH3-only molecules in cell cycle is more variable. BAD antagonizes both the cell cycle and antiapoptotic functions of BCL2 and BCL-x L through BH3 binding. BID has biochemically separable functions in apoptosis and S-phase checkpoint, determined by posttranslational modification. p53-induced PUMA is known only to have apoptotic function. Inhibition of apoptosis is oncogenic, whereas promotion of cell cycle arrest is tumor suppressive. Paradoxically, selected BCL2 family members can be both oncogenic and tumor suppressive. Which of the dual functions predominates is lineage specific and context dependent.

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“…However, Bcl-2 expression is not always correlated with accelerated oncogenesis and a poor outcome. Studies of human colon cancer (Ofner et al, 1995;Manne et al, 1997;Kaklamanis et al, 1998;Buglioni et al, 1999;Meterissian et al, 2001) and breast cancer (Silvestrini et al, 1994) demonstrated that increased Bcl-2 expression is associated with improved survival. In mice, Bcl-2 expression results in delayed tumor development including hepatocellular carcinoma (de la Coste et al, 1999), dimethylbenz(a)anthracene-induced mammary tumors (Murphy et al, 1999), and UV-or chemical-induced epidermal tumors (Rossiter et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Bcl-2 inhibition of T-cell proliferation is related to prolonged T-cell survival

et al. 2004

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Bcl-2 promotes oncogenesis by inhibiting cell death. Bcl-2 also inhibits proliferation and suppresses tumorigenesis in some settings. To clarify the role of the antiproliferative function of Bcl-2, mice expressing a mutant form of Bcl-2 reported to lack antiproliferative activity were generated (tyrosine 28 to alanine, Bcl-2-Y28A). As expected, both wild type (WT) and Bcl-2-Y28A inhibited apoptosis similarly. In contrast to previous results in cell lines, Bcl-2-Y28A inhibited T-cell proliferation identical to WTBcl-2. Significantly, both Bcl-2-Y28A and WT-Bcl-2 inhibited proliferation of T cells isolated from older animals, but not proliferation of T cells from immature mice. Instead, inhibition of cell activation correlated with T-cell size, p27 levels, and RNA content, all indicators of quiescent G0 arrest. Consistent with this model, Bcl-2 inhibition of T-cell proliferation was reversed by expression of Bax, again correlating cell proliferation with cell size. These experiments do not support genetically separate effects of Bcl-2 on apoptosis and proliferation. Instead, the data support a model in which Bcl-2 and Bax regulate T-cell proliferation by changes in T-cell size and by increasing the markers of quiescent G0 arrest. These changes likely result from prolonged T-cell survival.

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Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: Independent prognostic role of p53 and bcl-2

Cited by 93 publications

References 15 publications

Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis Is Inhibited by Bcl-2 but Restored by the Small Molecule Bcl-2 Inhibitor, HA 14-1, in Human Colon Cancer Cells

Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis Is Inhibited by Bcl-2 but Restored by the Small Molecule Bcl-2 Inhibitor, HA 14-1, in Human Colon Cancer Cells

BCL2 family in DNA damage and cell cycle control

Bcl-2 inhibition of T-cell proliferation is related to prolonged T-cell survival

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