Apoptosis regulators and their role in tumorigenesis.

Zörnig, Martin; Hueber, Anne-Odile; Baum, Wiebke; Evan, Gérard I.

doi:10.1016/s0002-9394(01)01388-5

Cited by 41 publications

(48 citation statements)

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“…We detected, however, no typical apoptotic cleavage patterns ( e.g. , of caspase 3 or PARP) in Western blot (data not shown), indicating that cells with lower TF expression did not undergo significantly more apoptosis in culture 59, 60, 61…”

Section: Discussionmentioning

confidence: 85%

Downregulation of tissue factor by RNA interference in human melanoma LOX‐L cells reduces pulmonary metastasis in nude mice

Wang

Amarzguioui

et al. 2004

Intl Journal of Cancer

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Tissue factor (TF), a transmembrane protein, initiates the blood coagulation cascade by complexing with its serine protease ligand factor VII(a) (FVIIa), ultimately leading to thrombin generation, fibrin deposition and platelet aggregation. TF is aberrantly expressed in many solid tumors and tumor cell lines 1-4 with higher expression levels in malignant tumor cells compared to their nonmalignant counterpart. Subsequent results suggested that TF participates in the tumor growth and dissemination of various cancers. 5 Clinically, TF expression strongly correlates with tumor progression. 6 -9 TF can promote tumor progression via coagulation-dependent or -independent mechanisms. 10,11 Activation of coagulation may trap tumor cells in a fibrin-platelet clot and allow local tumor growth, which is critically important for tumor dissemination and metastasis. 12,13 Moreover, several products of the coagulation system, including thrombin and fibrin, can stimulate angiogenesis, 13-15 which is necessary for tumor growth and metastasis. Independent of the downstream coagulation factors, FVIIa binding to TF can promote tumor-associated angiogenesis by upregulating angiogenic factors VEGF and IL-8. 16 -18 TF/FVIIa signaling resulting from the proteolytic activity of the complex is required for the upregulation of these angiogenic factors 19 -21 and for TF-dependent metastasis. 22 TF/FVIIa signaling has received widespread interest 10,[23][24][25][26] after the discovery of TF/FVIIa-induced calcium signals. 27 FVIIa/TF signaling, independent of the coagulation cascade, results in the upregulation of cytokines, growth factors 22,24 and induction of antiapoptosis, 28 which may contribute to tumor growth. Blocking TF function by administration of TF antibody or inactivated FVIIa has resulted in the reduced metastasis in murine metastasis models. 29,30 We have in this study used RNA interference specifically to knock down TF expression and investigated the effects on the metastatic capacity of human malignant melanoma cells.RNA interference (RNAi) is a process of sequence-specific posttranscriptional gene silencing triggered by double-stranded RNA. This phenomenon has been developed into a powerful technology to elucidate mammalian gene function by delivery of small interfering RNA (siRNA), duplexes of 19-21-nt RNA with 2-nt 3Ј overhangs, into cells. 31 Variable transfection efficiency and the transient nature of silencing by exogenously delivered siRNA limit the applicability of chemically synthesized siRNA in functional genomic studies. 32 Stable RNAi can be achieved in mammalian cells through RNA polymerase III-dependent expression of so-called short hairpin RNAs (shRNA) from integrated DNA constructs in stably transfected cells. 33,34 The transcribed shRNA is thought to be processed into siRNA-like molecules intracellularly. Studies from different cell types and against various genes have demonstrated the efficacy of endogenously expressed shRNA. 33,[35][36][37] In order to explore the potential role and possible mechanism o...

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Section: Discussionmentioning

confidence: 85%

Downregulation of tissue factor by RNA interference in human melanoma LOX‐L cells reduces pulmonary metastasis in nude mice

Wang

Amarzguioui

et al. 2004

Intl Journal of Cancer

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“…As in other tissues, homeostasis in the conjunctiva is essentially regulated by a delicate balance between cellular proliferation and cellular apoptosis. Thus, degenerative processes are linked to either decreased proliferative capacity or to increased apoptosis (Reed 1999; Zornig et al 2001). Previous investigations have shown that ageing is associated with apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis preventing genes are mainly represented by the Bcl‐2 family (Boise et al 1993; Reed 1994, 1998). Dysregulation of apoptosis‐related genes could be due to loss of caspases and/or overexpression of Bcl‐2, as seen in human tumour cell lines or neuroblastomas, and may contribute to the development of cancer (Reed 1999; Zornig et al 2001; Zhang & Herman 2002). Furthermore, the dysregulation of Fas expression and/or signalling (which triggers the normal apoptosis of keratinocytes) contributes to the pathogenesis of toxic epidermal necrolysis, acute cutaneous graft versus host disease, contact hypersensitivity or melanoma metastasis (Zornig et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Age‐related differential expression of apoptosis‐related genes in conjunctival epithelial cells

Giebel

Woenckhaus

Fabian

et al. 2005

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: To investigate whether the expression of apoptosis-related genes in normal conjunctival epithelial cells is age-related (as a prerequisite to assessing whether dysregulation of apoptosis may be involved during degenerative diseases). Methods: Differential expression of apoptosis-related genes (e.g. apoptosis protease-activating factor 1 [Apaf-1]; caspases [casp] 3, 5, 8 and 9; Bad, Bax, Bcl-2, Bim, c-myc, Bag-1, as well as p53) was assessed by reverse transcriptionpolymerase chain reaction (RT-PCR). Samples were obtained from impression cytology (IC) specimens taken from 50 healthy subjects. Group A comprised 27 subjects aged 19-32 years and group B included 23 subjects aged 53-84 years. Results: Reverse transcription-PCR revealed the detection of apoptosis-related m-RNAs as follows (group A compared to group B): Apaf-1 0%/0%; Bcl-2 0%/ 35%; Bim 0%/9%; Bag-1 0%/9%; p53 0%/4%; casp-3 11%/52%; casp-5 59%/48%; casp-8 44%/22%; casp-9 4%/9%; Bax 81%/52%; Bad 96%/ 56%, and c-myc 89%/96%. Conclusion: The data show an age-related expression of apoptosis-related genes such as casp-3, Bad, Bax and Bcl-2 in normal conjunctival cells. These results provide basic information which will help us understand the expression pattern of apoptotic genes during physiological ageing of the conjunctiva and the possible dysregulation of apoptotic genes during acute and chronic diseases such as dry eye disease, allergic conjunctivitis or cicatrizing conjunctivitis.

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“…Apoptosis has been well documented for its important role on embryogenesis,11 autoimmunity12 and tumorigenesis 13. Defects in apoptosis genes have been identified as causative or contributing pathogenetic factors.…”

mentioning

confidence: 99%

Single nucleotide polymorphism at Fas promoter is associated with cervical carcinogenesis

Lai

Sytwu

Sun

et al. 2002

Intl Journal of Cancer

101

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Apoptosis regulators and their role in tumorigenesis.

Cited by 41 publications

References 0 publications

Downregulation of tissue factor by RNA interference in human melanoma LOX‐L cells reduces pulmonary metastasis in nude mice

Downregulation of tissue factor by RNA interference in human melanoma LOX‐L cells reduces pulmonary metastasis in nude mice

Age‐related differential expression of apoptosis‐related genes in conjunctival epithelial cells

Single nucleotide polymorphism at Fas promoter is associated with cervical carcinogenesis

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