Unknown,Transcriptomics,Genomics,Proteomics

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Effect of HE4 overexpression or treatment with recombinant HE4 protein on OVCAR8 ovarian cancer cells

ABSTRACT: The ovarian cancer biomarker HE4 has been shown to have multiple effects on ovarian cancer pathogenesis. In order to reveal gene regulation upstream of HE4 biological effects in ovarian cancer, HE4 was overexpressed in OVCAR8 wild type ovarian cancer cells and compared to null vector transfected cells. To gain a more comprehensive understanding of HE4 effects and elucidate similarities/differences between short-term HE4 exposure versus stable overexpression, we also compared untreated wild type cells with cells exposed to recombinant HE4 protein.

ORGANISM(S): Homo sapiens

SUBMITTER: Jennifer Ribeiro

PROVIDER: E-MTAB-6366 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Ovarian cancer is one of the most common cancer among women in the world, and chemotherapy remains the principal treatment for patients. However, drug resistance is a major obstacle to the effective treatment of ovarian cancers and the underlying mechanism is not clear. An increased understanding of the mechanisms that underline the pathogenesis of drug resistance is therefore needed to develop novel therapeutics and diagnostic. Herein, we report the comparative analysis of the doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI/ADR-RES cells using integrated global proteomics and N-glycoproteomics. A total of 1525 unique N-glycosite-containing peptides from 740 N-glycoproteins were identified and quantified, of which 253 N-glycosite-containing peptides showed significant change in the NCI/ADR-RES cells. Meanwhile, stable isotope labeling by amino acids in cell culture (SILAC) based comparative proteomic analysis of the two ovarian cancer cells led to the quantification of 5509 proteins. As about 50% of the identified N-glycoproteins are low-abundance membrane proteins, only 44% of quantified unique N-glycosite-containing peptides had corresponding protein expression ratios. The comparison and calibration of the N-glycoproteome versus the proteome classified 14 change patterns of N-glycosite-containing peptides, including 8 up-regulated N-glycosite-containing peptides with the increased glycosylation sites occupancy, 35 up-regulated N-glycosite-containing peptides with the unchanged glycosylation sites occupancy, 2 down-regulated N-glycosite-containing peptides with the decreased glycosylation sites occupancy, 46 down-regulated N-glycosite-containing peptides with the unchanged glycosylation sites occupancy. Integrated proteomic and N-glycoproteomic analyses provide new insights, which can help to unravel the relationship of N-glycosylation and multidrug resistance (MDR), understand the mechanism of MDR, and discover the new diagnostic and therapeutic targets.

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Effect of HE4 overexpression or treatment with recombinant HE4 protein on OVCAR8 ovarian cancer cells

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