Unknown,Transcriptomics,Genomics,Proteomics

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Comparisons of the global gene profile between CLDN4-overexpressing and CLDN4-silencing ovarian cancer cells.

ABSTRACT: A microarray analysis was performed to compare the global gene expression profile between CLDN4-overexpressing (Control) and CLDN4-silencing SKOV-3 ovarian cancer cells. CLDN4 gene was knocked down by CLDN4 siRNA lentivirus. Total RNA was extracted and microarray was perfomed to compare the gene profiling changes between CLDN4-overexpressing (Control) and CLDN4-silencing cells. The experiment was performed in triplicate.

ORGANISM(S): Homo sapiens

SUBMITTER: Zhijian Gao

PROVIDER: E-GEOD-22493 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:With the onset of resistance, ovarian cancer cells display almost unpredictable adaptive potential. This may derive from genetic ancestry of the tumor cells and can be additionally tailored by post translational protein modifications (PTMs). The latter are profoundly shaped by the physical and chemical cues of the cancer microenvironment which, for ovarian cancer, is primarily the abdominal cavity. In this study, we took advantage of high-end proteome and phosphoproteome analyses combined with multiparametric morphometric profiling for the description of the proteome signatures of high-grade serous carcinomas (OVCAR-3) and non-serous carcinomas (SKOV-3) ovarian cancer cells. For the functional experiments, we applied two different protocols, representing typical stimuli of the peritoneal cavity and of the growing tumor mass: on the one side hypoxia (oxygen 1%) which develops within the tumor mass or is experienced during migration/extravasation in non-vascularized tissues. For comparison, fluid shear stress (2.8 dyn/cm2, orbital shaker method) which characterizes the tumor surface in peritoneal cavity or metastases spread in the bloodstream. After 3 hours incubation, treatment groups were clearly distinguishable by PCA analysis. Whereas basal proteome profile of SKOV-3 and OVCAR-3 cells appeared almost unchanged, phosphoproteome analysis revealed multiple regulations. These affected primarily cellular structure and proliferative potential and consolidated after 24h treatment. Albeit maintaining their individuality, hypoxia modified cell metabolism and morphology of both OVCAR-3 and SKOV-3: upon oxygen reduction cell size increased in concerted regulation of pathways related to Rho-GTPases and/or cytoskeletal elements (proteome and phosphoproteome). Also shear stress stimulation sharpened the response profile of SKOV-3 and OVCAR-3: this retraced their pathophysiological behavior and actively modified structural proteins as well as metabolism (e.g. delta(14)-sterol reductase, Kinesin-like proteins (KIF-22/20A) and Actin-related protein 2/3 complex). In conclusion, we characterized a biochemical and structural fingerprinting describing the adaptive potential of ovarian cancer cells to physical/chemical stressors typical for the abdominal cavity.

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Comparisons of the global gene profile between CLDN4-overexpressing and CLDN4-silencing ovarian cancer cells.

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