Apoptosis Induction by Activator Protein 2α Involves Transcriptional Repression of Bcl-2

Wajapeyee, Narendra; Britto, Ramona; Ravishankar, Halasahalli M.; Somasundaram, Kumaravel

doi:10.1074/jbc.m600539200

Cited by 54 publications

(46 citation statements)

References 54 publications

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“…This original result, potentially relevant for pancreatic cancer therapy in which gemcitabine is the first-line treatment, was however expected as AP-2a was previously shown to increase colon cancer cell sensitivity to chemotherapy. This effect was independent of p53 (Wajapeyee et al, 2005) and resulted from a downregulation of Bcl-2 and an induction of apoptosis (Wajapeyee et al, 2006). Moreover, the same group also showed that AP-2 was induced by a post-transcriptional mechanism by various chemotherapeutic agents such as adriamycin or cisplatin.…”

Section: Discussionmentioning

confidence: 70%

Tumour growth and resistance to gemcitabine of pancreatic cancer cells are decreased by AP-2α overexpression

et al. 2009

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BACKGROUND: Activator protein-2a (AP-2a) is a transcription factor that belongs to the family of AP-2 proteins that have essential roles in tumorigenesis. Indeed, AP-2a is considered as a tumour-suppressor gene in different tissues such as colonic, prostatic or breast epithelial cells. Moreover, AP-2a also participates in the control of colon and breast cancer cells sensitivity towards chemotherapeutic drugs. Despite its potential interest, very few data are available regarding the roles of AP-2a in pancreatic cancer. METHODS: We have developed a stable pancreatic CAPAN-1 cell line overexpressing AP-2a. Consequences of overexpression were studied in terms of in vivo cell growth, gene expression, migration capacity and chemosensitivity. RESULTS: In vivo tumour growth of CAPAN-1 cells overexpressing AP-2a was significantly decreased by comparison to control cells. An altered expression pattern of cell cycle-controlling factors (CDK-4, CDK-6, cyclin-G1, p27 kip1 and p57

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Section: Discussionmentioning

confidence: 70%

Tumour growth and resistance to gemcitabine of pancreatic cancer cells are decreased by AP-2α overexpression

et al. 2009

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“…The expression of AP-2 is tissue-and cell-specific. AP-2␣ and AP-2␥ have been shown to be capable of controlling the expression of many cancer-related genes such as HER-2 (26), p21 (27), c-kit (28), bcl-2 (29), vascular endothelial growth factor (30), MUC18 (31), and p53 (32). Recent studies have also shown that AP-2␣ and AP-2␥ have tumor-suppressive activity in breast cancer, melanoma, and prostate cancer cells (30,(32)(33)(34)(35)(36)(37)(38).…”

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confidence: 99%

Tumor-specific Activation of Human Telomerase Reverses Transcriptase Promoter Activity by Activating Enhancer-binding Protein-2β in Human Lung Cancer Cells

Deng

Jayachandran

et al. 2007

Journal of Biological Chemistry

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The up-regulated expression and telomerase activity of human telomerase reverse transcriptase (hTERT) are hallmarks of tumorigenesis. The hTERT promoter has been shown to promote hTERT gene expression selectively in tumor cells but not in normal cells. However, little is known about how tumor cells differentially activate hTERT transcription and induce telomerase activity. In this study, we identified activating enhancerbinding protein-2␤ (AP-2␤) as a novel transcription factor that specifically binds to and activates the hTERT promoter in human lung cancer cells. AP-2␤ was detected in hTERT promoter DNA-protein complexes formed in nuclear extracts prepared only from lung cancer cells but not from normal cells. We verified the tumor-specific binding activity of AP-2␤ for the hTERT promoter in vitro and in vivo and detected high expression levels of AP-2␤ in lung cancer cells. We found that ectopic expression of AP-2␤ reactivated hTERT promoter-driven reporter green fluorescent protein (GFP) gene and endogenous hTERT gene expression in normal cells, enhanced GFP gene expression in lung cancer cells, and prolonged the life span of primary lung bronchial epithelial cells. Furthermore, we found that inhibition of endogenous AP-2␤ expression by AP-2␤ gene-specific small interfering RNAs effectively attenuated hTERT promoter-driven GFP expression, suppressed telomerase activity, accelerated telomere shortening, and inhibited tumor cell growth by induction of apoptosis in lung cancer cells. Our results demonstrate the tumor-specific activation of the hTERT promoter by AP-2␤ and imply the potential of AP-2␤ as a novel tumor marker or a cancer therapeutic target.Telomerase is an RNA-dependent DNA polymerase ribonucleoprotein enzyme that synthesizes telomeres after cell division and maintains chromosomal stability, leading to cellular immortalization (1, 2). It comprises a template-containing RNA component and a human telomerase reverse transcriptase (hTERT) 2 in humans (3-6). The high activity of telomerase has been implicated in cellular immortalization, transformation, and oncogenesis. Most normal somatic cells do not display telomerase activity, whereas a high level of telomerase activity is detected in germinal cells, immortalized cell lines, and 85-90% of human cancer specimens (7-13). hTERT is the catalytic subunit of telomerase (4, 5). The elevated expression of hTERT is necessary to transform normal human cells into cancer cells and is regarded as a hallmark of tumorigenesis (14). The hTERT promoter has been showed to be capable of promoting both constitutive hTERT gene and transgene expression selectively in tumors but not in normal cells (15)(16)(17). This is largely attributed to the unique ability of tumor cells to up-regulate hTERT transcription. The expression of hTERT is tightly regulated by various cellular factors. For example, expression of c-Myc has been shown to induce the expression of hTERT, whereas the expression of SP1 (stimulating protein-1) suppresses it (18,19). Two E-boxes and an activating en...

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“…In keratinocytes, AP-2α functions in developmental events associated with growth and differentiation and plays a key role in keratinocyte specific gene expression [22,33]. The presence of supra-physiological levels of AP-2α has been shown to block cell cycle progression [34] and induce cellular apoptosis [23,35]; thus evading attempts at stable transfection. Consequently overexpression studies of AP-2α in cell culture model systems have been limited to transient transfections.…”

Section: Generation and Characterization Of Tmk-ap2 Stable Clonesmentioning

confidence: 99%

Development of an inducible gene expression system for primary murine keratinocytes

Nagarajan¹,

Sinha²

2008

Journal of Dermatological Science

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Background-The tetracycline (Tet) responsive system is a valuable tool that is routinely used in a wide variety of mammalian cells for regulatable expression of gene products. However, technical difficulties such as harsh selection conditions and extensive screening processes to identify suitably responsive clones limit the generation of stable cell lines. Hence, application of this system in mammalian cells with relatively slow growth rates and / or the capacity to undergo terminal differentiation such as primary mouse keratinocytes is particularly challenging.

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Apoptosis Induction by Activator Protein 2α Involves Transcriptional Repression of Bcl-2

Cited by 54 publications

References 54 publications

Tumour growth and resistance to gemcitabine of pancreatic cancer cells are decreased by AP-2α overexpression

Tumour growth and resistance to gemcitabine of pancreatic cancer cells are decreased by AP-2α overexpression

Tumor-specific Activation of Human Telomerase Reverses Transcriptase Promoter Activity by Activating Enhancer-binding Protein-2β in Human Lung Cancer Cells

Development of an inducible gene expression system for primary murine keratinocytes

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