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dc.contributor.authorSyed, Viqar
dc.contributor.authorZhang, Xiang
dc.contributor.authorLau, Kin-Mang
dc.contributor.authorCheng, Robert Y. S.
dc.contributor.authorMukherjee, Kasturi
dc.contributor.authorHo, Shuk-Mei
dc.date2022-08-11T08:08:49.000
dc.date.accessioned2022-08-23T16:09:17Z
dc.date.available2022-08-23T16:09:17Z
dc.date.issued2005-08-24
dc.date.submitted2009-01-13
dc.identifier.citationOncogene. 2005 Dec 8;24(55):8128-43. <a href="http://dx.doi.org/10.1038/sj.onc.1208959">Link to article on publisher's site</a>
dc.identifier.issn0950-9232 (Print)
dc.identifier.doi10.1038/sj.onc.1208959
dc.identifier.pmid16116479
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32658
dc.description.abstractEstrogens regulate normal ovarian surface epithelium (OSE) cell functions but also affect epithelial ovarian cancer (OCa) development. Little is known about how estrogens play such opposing roles. Transcriptional profiling using a cDNA microarray containing 2400 named genes identified 155 genes whose expression was altered by estradiol-17beta (E2) in three immortalized normal human ovarian surface epithelial (HOSE) cell lines and 315 genes whose expression was affected by the hormone in three established OCa (OVCA) cell lines. All but 19 of the genes in these two sets were different. Among the 19 overlapping genes, five were found to show discordant responses between HOSE and OVCA cell lines. The five genes are those that encode clone 5.1 RNA-binding protein (RNPS1), erythrocyte adducin alpha subunit (ADD1), plexin A3 (PLXNA3 or the SEX gene), nuclear protein SkiP (SKIIP), and Rap-2 (rap-2). RNPS1, ADD1, rap-2, and SKIIP were upregulated by E2 in HOSE cells but downregulated by estrogen in OVCA cells, whereas PLXNA3 showed the reverse pattern of regulation. The estrogen effects was observed within 6-18 h of treatment. In silicon analyses revealed presence of estrogen response elements in the proximal promoters of all five genes. RNPS1, ADD1, and PLXNA3 were underexpressed in OVCA cell lines compared to HOSE cell lines, while the opposite was true for rap-2 and SKIIP. Functional studies showed that RNPS1 and ADD1 exerted multiple antitumor actions in OVCA cells, while PLXNA3 only inhibited cell invasiveness. In contrast, rap-2 was found to cause significant oncogenic effects in OVCA cells, while SKIIP promotes only anchorage-independent growth. In sum, gene profiling data reveal that (1) E2 exerts different actions on HOSE cells than on OVCA cells by affecting two distinct transcriptomes with few overlapping genes and (2) among the overlapping genes, a set of putative oncogenes/tumor suppressors have been identified due to their differential responses to E2 between the two cell types. These findings may explain the paradoxical roles of estrogens in regulating normal and malignant OSE cell functions.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=16116479&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1038/sj.onc.1208959
dc.subjectCell Line; Cell Line, Transformed; Cell Line, Tumor; Epithelial Cells; Estrogens; Female; Gene Expression Profiling; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Human papillomavirus 6; Humans; Oligonucleotide Array Sequence Analysis; Ovarian Neoplasms; Ovary; Transcription, Genetic
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleProfiling estrogen-regulated gene expression changes in normal and malignant human ovarian surface epithelial cells
dc.typeJournal Article
dc.source.journaltitleOncogene
dc.source.volume24
dc.source.issue55
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1217
dc.identifier.contextkey693127
html.description.abstract<p>Estrogens regulate normal ovarian surface epithelium (OSE) cell functions but also affect epithelial ovarian cancer (OCa) development. Little is known about how estrogens play such opposing roles. Transcriptional profiling using a cDNA microarray containing 2400 named genes identified 155 genes whose expression was altered by estradiol-17beta (E2) in three immortalized normal human ovarian surface epithelial (HOSE) cell lines and 315 genes whose expression was affected by the hormone in three established OCa (OVCA) cell lines. All but 19 of the genes in these two sets were different. Among the 19 overlapping genes, five were found to show discordant responses between HOSE and OVCA cell lines. The five genes are those that encode clone 5.1 RNA-binding protein (RNPS1), erythrocyte adducin alpha subunit (ADD1), plexin A3 (PLXNA3 or the SEX gene), nuclear protein SkiP (SKIIP), and Rap-2 (rap-2). RNPS1, ADD1, rap-2, and SKIIP were upregulated by E2 in HOSE cells but downregulated by estrogen in OVCA cells, whereas PLXNA3 showed the reverse pattern of regulation. The estrogen effects was observed within 6-18 h of treatment. In silicon analyses revealed presence of estrogen response elements in the proximal promoters of all five genes. RNPS1, ADD1, and PLXNA3 were underexpressed in OVCA cell lines compared to HOSE cell lines, while the opposite was true for rap-2 and SKIIP. Functional studies showed that RNPS1 and ADD1 exerted multiple antitumor actions in OVCA cells, while PLXNA3 only inhibited cell invasiveness. In contrast, rap-2 was found to cause significant oncogenic effects in OVCA cells, while SKIIP promotes only anchorage-independent growth. In sum, gene profiling data reveal that (1) E2 exerts different actions on HOSE cells than on OVCA cells by affecting two distinct transcriptomes with few overlapping genes and (2) among the overlapping genes, a set of putative oncogenes/tumor suppressors have been identified due to their differential responses to E2 between the two cell types. These findings may explain the paradoxical roles of estrogens in regulating normal and malignant OSE cell functions.</p>
dc.identifier.submissionpathgsbs_sp/1217
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentDepartment of Surgery
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages8128-43


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