Modulation of cellular apoptotic potential: contributions to oncogenesis

Stambolic, Vuk; Mak, Tak W.; Woodgett, James R.

doi:10.1038/sj.onc.1203126

Cited by 113 publications

(69 citation statements)

References 126 publications

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“…43 It is certain that reduced expression of PTEN results in unopposed PKB activation, which can effect either cell cycle arrest (probably mediated through up-regulation of p27 KIP1 ), 44 or increased survival (through multiple anti-apoptotic pathways). 40,45 Immunohistochemical analysis of PTEN expression is a powerful tool by which one can evaluate its role in human malignancies. This has been conducted for several human cancers such as prostate, 46 thyroid, 47 endometrial, 48 melanoma, 49 ovarian 50 and gastric 51 carcinomas, to name a few.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated PTEN‐PKB and negative receptor status in human breast cancer

Shi

Zhang

Pintilie

et al. 2003

Intl Journal of Cancer

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Recent studies demonstrate that abnormalities in PTEN may be one of the most frequent genetic events observed in human cancers. PTEN dysfunction leads to tumorigenesis through unopposed survival signals mediated via activated protein kinase B (PKB), which may also be associated with hormone-independence. We therefore investigated the relationship between PTEN-PKB and receptor status in human breast cancer. Several molecular variables, including immunohistochemical staining for PTEN, PKB (phosphorylated on ser473), p53 and p21 were evaluated. The p53 gene was sequenced from exons 2-11. Seventy-eight participants in a randomised breast cancer trial served as the cohort for our study. Twenty-eight of 77 (36%) patients' tumours demonstrated absent or reduced PTEN expression; 17 of 78 (22%) tumours over-expressed P-PKB. A significant inverse relationship was observed between reduced PTEN and increased P-PKB expression. Reduced PTEN also correlated with reduced ER or PR expression. None of the molecular variables correlated with survival. ER and PR negative tumours, however, experienced a significantly inferior disease-free survival than other ER/PR status tumours. Immunohistochemical analyses of ER expression in mammary carcinomas arising in PTEN heterozygous knockout mice did not demonstrate a reduction in ER immunoreactivity, in comparison to wildtype mice. Our data demonstrate that the PTEN-PKB pathway is abnormal in approximately 1 ⁄3 of lymph node negative breast cancer. Dysregulated PTEN-PKB was also associated with reduced ER/PR expression, but this does not appear to be a simple direct causal relationship. These observations support the contention that dysregulation in PTEN-PKB contributes to disease progression and hormone resistance of human breast cancer.

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Section: Discussionmentioning

confidence: 99%

Dysregulated PTEN‐PKB and negative receptor status in human breast cancer

Shi

Zhang

Pintilie

et al. 2003

Intl Journal of Cancer

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“…12,13 Similarly, cells that have DNA damage undergo apoptosis. [14][15][16][17] This eliminates cells that have accrued genetic mutations and may thereby become cancerous.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, induction of apoptosis is the mode of action of many anti-tumor chemotherapeutic agents that are currently in use. [14][15][16][17] …”

Section: Introductionmentioning

confidence: 99%

Suppression of apoptosis: role in cell growth and neoplasia

White

McCubrey

2001

Leukemia

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A cell is a potentially dangerous thing. In unicellular organisms, cells divide and multiply in a manner that is chiefly determined by the availability of nutritional substrates. In a multicellular organism, each cell has a distinct growth potential that is designed to subsume a role in the function of the whole body. Departure from this path to one of uncontrolled cellular proliferation leads to cancer. For this reason, evolution has endowed cells with an elaborate set of systems that cause errant cells to self-destruct. This process of cell suicide is known as apoptosis or programmed cell death and it plays a crucial role in the growth of both normal and malignant cells. In this review, we describe the mechanisms whereby programmed cell death is induced and executed. In particular, we concentrate on how anti-apoptotic signals generated by cytokines promote cell survival and how these signal transduction pathways may be involved in the pathogenesis of neoplasia. Understanding how these processes contribute to tumorigenesis may suggest new therapeutic options. Leukemia (2001) 15, 1011-1021.

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“…Virus-infected cells are eliminated by the interaction with cytotoxic T-lymphocytes that kill the virus-infected cells by inducing apoptosis (Shibata et al, 1994;Darmon et al, 1995). Cells that have DNA damage undergo apoptosis so as to eliminate cells that have accumulated genetic mutations and may become cancerous (Jaattela, 1999;Stambolic et al, 1999). In addition to being activated during developmentrelated cell reduction, apoptosis can be triggered in many cell types by various stresses.…”

mentioning

confidence: 99%

Nuclear Factor-κB Activation: A Question of Life or Death

Shishodia¹,

Aggarwal²

2002

BMB Reports

206

168

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Apoptosis is a mode of cell death that plays an important role in both pathological and physiological processes. Research during the last decade has delineated the entire machinery needed for cell death, and its constituents were found to pre-exist in cells. The apoptotic cascade is triggered when cells are exposed to an apoptotic stimulus. It has been known for several years that inhibitors of protein synthesis can potentiate apoptosis that is induced by cytokines and other inducers. Until 1996, it was not understood why protein synthesis inhibitors potentiate apoptosis. Then three reports appeared that suggested the role of the transcription factor NF-κB activation in protecting the cells from TNF-induced apoptosis. Since then several proteins have been identified that are regulated by NF-κB and are involved in cell survival, proliferation, and protection from apoptosis. It now seems that when a cell is attacked by an apoptotic stimulus, the cell responds first by activating anti-apoptotic mechanisms, which may or may not be followed by apoptosis. Whether or not a cell undergoes proliferation, the survival, or apoptosis, appears to involve a balance between the two mechanisms. Inhibitors of protein synthesis seem to suppress the appearance of protein that are involved in anti-apoptosis. The present review discusses how NF-κB controls apoptosis.

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Modulation of cellular apoptotic potential: contributions to oncogenesis

Cited by 113 publications

References 126 publications

Dysregulated PTEN‐PKB and negative receptor status in human breast cancer

Dysregulated PTEN‐PKB and negative receptor status in human breast cancer

Suppression of apoptosis: role in cell growth and neoplasia

Nuclear Factor-κB Activation: A Question of Life or Death

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