Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transfection of HaCaT cells with HPV11 HPV16 or HPV45 genome

ABSTRACT: We investigated the early stage of HPV infections by global expression profiling in a cell model, in which cells from the human keratinocyte cell line, HaCaT, were transfected with HPV11, HPV16 or HPV45 genomes ( methods used for transfection are described in PubMed ID: 21078297)

ORGANISM(S): Homo sapiens

SUBMITTER: Bogumil Kaczkowski

PROVIDER: E-MTAB-1160 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Integrative analyses reveal novel strategies in HPV11,-16 and -45 early infection.

Kaczkowski Bogumil B Rossing Maria M Andersen Ditte K DK Dreher Anita A Morevati Marya M Visser Melissa A MA Winther Ole O Nielsen Finn Cilius FC Norrild Bodil B

Scientific reports 20120717

The interaction between human papillomavirus (HPV) and host cells is not well understood. We investigate the early stage of HPV infections by global expression profiling in a cell model, in which HaCaT cells were transfected with HPV11, HPV16 or HPV45 genomes. We report the differential expression of genes not previously implicated in HPV biology, such as the PSG family and ANKRD1, and of genes implicated in the biology of other viruses, e.g. MX1, IFI44 and DDX60. Carcinogenesis-related genes, e ...[more]

PMID: 22808421

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Project description:The objective of this study was to elucidate the role of Nupr1 in pancreatic tumorigenesis. Using the Pdx-1-cre;LSL-KrasG12D mouse as model we discovered that, in contrast to KrasG12D pancreas that develop multiple foci of pancreatic intraepithelial neoplasia (PanIN), KrasG12D;Nupr1KO pancreas were free from such lesions, indicating that Nupr1 is pivotal for PanIN formation. In vitro, MiaPaCa2 cells activated Nupr1 expression in response to nutrient deprivation and this expression was necessary for cell survival. Mechanistically, Nupr1 protected cells from stress-induced death by inhibiting apoptosis through an alternative RelBàIER3-dependent pathway and independent from activation of the classical RelA-based NF-kB pathway. In agreement with these findings, Nupr1, RelB and IER3 proteins were found co-expressed in PanINs from KrasG12D pancreas. Moreover, pancreas-specific KrasG12D;RelbDpanc mice displayed a delay in PanIN development associated with a lack of IER3 expression, further emphasizing the relevance of this pathway in vivo. Efficient PanIN formation was therefore dependent on the expression of Nupr1 and RelB, with the probable involvement of IER3. Finally, a significant correlation between expression of Nupr1, RelB and IER3 and a poor prognosis of patients with PDAC was found. Altogether, our results reveal a novel stress-related pathway that requires the functional interaction of Nupr1àRelBàIER3 in KrasG12D-dependent transformation of the pancreas and expand our understanding of the molecular machinery that mediates the early steps of pancreatic carcinogenesis. Since Nupr1 belongs to the HMG family of chromatin remodelers with transcriptional co-factor activity, Nupr1 could increase cell survival in a nutrient-deprived microenvironment by activating the expression of pro-survival genes. Moreover, considering that RelB, and not RelA/p65, is essential to the Nupr1-mediated survival mechanism that takes place upon nutrient deprivation-induced stress, we made the hypothesis that the two NF-kB transcription factors should activate different sets of genes among which a pivotal pro-survival gene would be exclusively dependent on RelB. In order to test this two hypothesis, an Affymetrix microarray analysis was performed using pancreatic cancer cells transfected with siCtrl or siNupr1 and cultured for 3, 6 or 9 hrs in EBSS; or transfected with siRelB, siRelA/p65 or siCtrl and cultured for 9 hrs in EBSS or Mock.

Dataset Information

Transfection of HaCaT cells with HPV11 HPV16 or HPV45 genome

Publications

Integrative analyses reveal novel strategies in HPV11,-16 and -45 early infection.

Similar Datasets

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