This SuperSeries is composed of the SubSeries listed below.
Integrative survival-based molecular profiling of human pancreatic cancer.
Specimen part, Disease, Disease stage
View SamplesTo perform an integrative profile of human pancreatic cancer (PDAC) to identify prognosis-significant genes and their related pathways.
Integrative survival-based molecular profiling of human pancreatic cancer.
Specimen part, Disease, Disease stage
View SamplesRetinoblastoma gene (Rb1) is required for proper cell cycle exit in the developing mouse inner ear and its deletion in the embryo leads to proliferation of sensory progenitor cells that differentiate into hair cells and supporting cells. In the Pou4f3-Cre:Rb1 flox/flox (Rb1 cKO) inner ear, utricular hair cells differentiate and survive into adulthood whereas differentiation and survival of cochlear hair cells are impaired. To comprehensively survey the pRb pathway in the mammalian inner ear, we performed microarray analysis of Rb1 cKO cochlea and utricle.
Overlapping and distinct pRb pathways in the mammalian auditory and vestibular organs.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Loss of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) induces apoptotic processes in pancreatic carcinoma cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcription factor and microRNA interactions in lung cells: an inhibitory link between NK2 homeobox 1, miR-200c and the developmental and oncogenic factors Nfib and Myb.
Cell line, Treatment
View SamplesEarly invasive growth and metastasis are features of pancreatic cancer that rely on resistance to anoikis, an apoptosis program activated upon loss of adequate matrix anchorage. Re-expression of the tumor suppressor p16 reversed anoikis resistance of pancreatic cancer cells. This conversion to an anoikis-susceptible phenotype was found to be associated with a striking loss of GNE mRNA expression, prompting us to address the role of GNE in pancreatic cancer in more detail. GNE catalyzes a rate-limiting key step of the sialic acid biosynthesis and may have additional functions in the nucleus.
Loss of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) induces apoptotic processes in pancreatic carcinoma cells.
Specimen part, Cell line
View SamplesEarly invasive growth and metastasis are features of pancreatic cancer that rely on resistance to anoikis, an apoptosis program activated upon loss of adequate matrix anchorage. Re-expression of the tumor suppressor p16 reversed anoikis resistance of pancreatic cancer cells. This conversion to an anoikis-susceptible phenotype was found to be associated with a striking loss of GNE mRNA expression, prompting us to address the role of GNE in pancreatic cancer in more detail. GNE catalyzes a rate-limiting key step of the sialic acid biosynthesis and may have additional functions in the nucleus.
Loss of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) induces apoptotic processes in pancreatic carcinoma cells.
Specimen part, Cell line
View SamplesCell-specific gene expression is achieved by a combination of mechanisms including transcriptional and post-transcriptional regulation. The transcription factor Nkx2-1, essential for lung cell differentiation, mainly acts in transcriptional activation but can directly or indirectly repress gene expression. microRNAs are a class of small non-coding RNA that control one of the major mechanisms of gene repression. To identify miRNAs regulated by Nkx2-1 that may mediate its repressing effects, we knocked-down Nkx2-1 in mouse lung epithelial cell lines and systematically identified targets by genome-wide miR and mRNA expression analyses. Nkx2-1 controls expression of miRs known to contribute to lung cell differentiation in development and disease and others not previously described. Amongst the significantly altered miRs, the mir-106a-363 cluster, miR-1195, miR-378, and miR-346 are directly correlated with the levels of Nkx2-1, whereas miR-200c/b, miR-221, and miR- 222 are inversely correlated. These miRNAs are expressed in embryonic lung at day E11.5, and/or E19.5 determined by in-situ hybridization. Expression of predicted targets of mir-1195, mir-346 and miR-200c and mir-221/222 were evaluated by mRNA expression microarrays in Nkx2-1 knockdown cells identifying those anti-correlated to the corresponding miRNA expression. Genes regulated by mir-1195, Cyp2s1 and Map3k2, by mir-346, Klf6, and miR-200c, Myb, Nfib, and Six1, were validated by qRT-PCR. Inhibition of mir-1195 confirms the inverse correlation of this miRNA with its putative targets Cyp2s1 and Map3k2. This miRNA-mRNA expression analysis identifies potential paths of Nkx2-1 mediated gene repression, and contributes to the understanding of gene regulation in lung epithelial differentiation and development.
Transcription factor and microRNA interactions in lung cells: an inhibitory link between NK2 homeobox 1, miR-200c and the developmental and oncogenic factors Nfib and Myb.
Cell line, Treatment
View SamplesHere we report the characterization of a novel role for the retinoblastoma protein (pRb) as a regulator of osteoblast adhesion. Abrogation of pRb in osteoblasts resulted in aberrant cadherin expression and loss of adherens junctions. This produced defects suggestive of a transformed phenotype such as impaired cell-to-cell adhesion, loss of contact-dependent growth arrest, and the capacity to evade anoikis. This also resulted in profound abnormalities in bone structure. Consistent with this, microarray analyses showed that pRb regulates a wide repertoire of osteoblast cell adhesion genes. In addition, pRb loss also resulted in altered expression and function of several known regulators of cellular adhesion and adherens junction assembly, such as the Rho GTPase Rac1 and the merlin tumor suppressor. Taken together, our results show that pRb controls cell adhesion by regulating the expression and adherens junction components and by regulating the function of molecules involved in adherens junction assembly and stability.
A role for the retinoblastoma protein as a regulator of mouse osteoblast cell adhesion: implications for osteogenesis and osteosarcoma formation.
Specimen part
View SamplesObservational studies in human suggest involvement of vitamin A/retinoic acid (RA) signaling in the regulation of airway smooth muscle (ASM) function, but the precise mechanisms by which RA impacts ASM phenotype is not clear. Here, we generated trascriptional profiles from two different models of RA-sufficient and RA-deficient mouse ASM in order to determine the molecular targets of RA in ASM (VAS/VAD, CTR/BMS)
Retinoic acid signaling is essential for airway smooth muscle homeostasis.
Specimen part
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