Expression microarray analysis of HaCaT epidermal keratinocyte treated with AdcaRAS/dnRAS, p53 siRNA, and/or TGF-beta
Ontology highlight
ABSTRACT: We demonstrate that activation of Ras and TGF-β pathways strengthens the binding of p63 to its genomic sites and modulates the expression of p63 target genes. Our findings support a model of mutual inhibition between ΔNp63α, DUSP6 and mutant p53 downstream of oncogenic Ras and TGF-β.
Project description:TGF-beta is one of the key cytokines implicated in various disease processes including cancer. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells and in contrast, acts as a pro-tumour cytokine by promoting tumour angiogenesis, immune-escape and metastasis. The effect of TGF-beta on the regulation of gene expression is cell-type specific. In order to identify TGF-beta regulated genes in different cell-types, we followed the expression profiling approach. Keywords: cell type specific response to TGF-beta
Project description:p63, a member of p53 family, is transcribed in different variants, containing (TA) or lacking (ΔN) the N-terminal transactivation domain. Although the proteins of p53 family share high sequence and structural similarities, distinct functions for p63 are emerging. Here we provided a quantitative proteomic analysis by stable isotope dimethyl labeling of colon cancer stem cells over-expressing ΔNp63α in order to investigate the cellular pathways modulated by this p63 isoform.
Project description:p63, a homologue of the tumor suppressor p53, is critical for the development and maintenance of squamous epithelia. p63 is specifically expressed in the basal layers of stratified epithelial tissues, and is considered to be a specific marker for cells of this type. The role of p63 in tumorigenesis remains poorly defined. Numerous studies have highlighted the oncogenic potential of the predominant p63 isoform, ΔNp63α; however, data suggests that other p63 proteins can act as tumor suppressors or alter the metastatic potential of tumors. ΔNp63α can act as a transcriptional repressor, but the link between the transcriptional functions of p63 and its biological role is still unclear. In this study, we used a loss-of-function approach to investigate the transcriptional programs controlled by p63. Keywords: cell line panel
Project description:RIE (rat intestinal epithelial) cells treated with 2 ng/ml of TGF-beta-1 for 1 hr were compared to control cells. The experiment was performed under identical conditions four times: RIE vs RIE - TGF-beta #1-#4. RIE-Ras cells were established by stable transfection of the parental cells with pSV2-H-Ras(12V) which contain human sequences encoding the constitutively active H-Ras(12V) protein. RIE-Ras cells treated with 2 ng/ml of TGF-beta-1 for 1 hr were compared to control cells. The experiment was performed four times under identical conditions (RIE-Ras vs RIE-RAS TGF-beta #1-#4).
Project description:RIE (rat intestinal epithelial) cells treated with 2 ng/ml of TGF-beta-1 for 1 hr were compared to control cells. The experiment was performed under identical conditions four times: RIE vs RIE - TGF-beta #1-#4. RIE-Ras cells were established by stable transfection of the parental cells with pSV2-H-Ras(12V) which contain human sequences encoding the constitutively active H-Ras(12V) protein. RIE-Ras cells treated with 2 ng/ml of TGF-beta-1 for 1 hr were compared to control cells. The experiment was performed four times under identical conditions (RIE-Ras vs RIE-RAS TGF-beta #1-#4). Keywords = TGF-beta Keywords = rat Keywords = intestinal epithelial cells Keywords: parallel sample
Project description:TGF-beta signaling is required for the differentiation of gut-resident memory CD8 T cells. Here, we showed that the deficiency of transcription factor T-bet partially rescued the differentiation of TGF-beta receptor deficient gut-resident memory CD8 T cells. Hic1 induction further strengthens TRM maturation in the absence of TGF-b and T-bet.
Project description:MCF7 is a breast adenocarcinoma cell line which exhibits properties of differentiated luminal epithelial cells. ΔNp63α, an N-terminally truncated isoform of p51/p63 protein, plays a critical role in mammary gland development. Here, we inducibly express ΔNp63α in MCF7 cells and studied its role in stemness of breast cancer cells.
Project description:MCF7 is a breast adenocarcinoma cell line which exhibits properties of differentiated luminal epithelial cells. ΔNp63α, an N-terminally truncated isoform of p51/p63 protein, plays a critical role in mammary gland development. Here, we inducibly express ΔNp63α in MCF7 cells and studied its role in stemness of breast cancer cells.
Project description:Epithelial-to-mesenchymal transitions (EMT) play prominent roles during development, regeneration and tumor progression. EMTs are triggered by TGF-β, RAS and other signals that cooperatively induce the expression of master EMT transcription factors such as SNAIL. Here, we elucidate how the TGF-β and RAS pathways jointly trigger EMTs and tie them to broader developmental programs. We identify RAS response element binding protein 1 (RREB1) as a critical partner of TGF-β-activated SMAD transcription factors in driving SNAIL expression and EMT program in mammary gland epithelial cells.