Expression of R-ras oncogenes in the hermaphroditic fish Kryptolebias marmoratus, exposed to endocrine disrupting chemicals.
The hermaphroditic fish Krytolebias marmoratus is a potential fish model for study of tumour development. Recently, sequences and expression of some oncogenes and tumor suppressor gene have been studied in K. marmoratus. To get a better understanding of oncogene expression at different development stage, and in different tissues three R-ras genes were cloned and fully sequenced. Expression of these R-ras genes (R-ras1, R-ras2, R-ras3) was also studied in fish exposed to endocrine-disrupting chemicals (EDCs). Liver showed the highest level of expression compared to other tissues, even though each R-ras gene showed different expression patterns in tissues. Interestingly, in secondary male (ovary atresia stage), expression levels of three R-ras genes was lower compared to hermaphrodites. At different developmental stages, R-ras2 gene showed most pronounced expression at early embryogenesis but at stage 5 (hatchling stage) and juvenile stage, R-ras3 gene showed the highest expression. After the juvenile stage, R-ras1 gene was upregulated compared to other R-ras genes, which showed the highest expression at the hermaphroditic stage. When fish were exposed to 17-beta-estradiol (E2), a natural estrogen and tamoxifen, a nonsteroidal estrogen antagonist and three EDCs viz., 4-n-nonylphenol (NP), bisphenol A (BPA), and 4-tert-octylphenol (OP), all the three R-ras genes were induced, except in the fish exposed to tamoxifen. These results suggest that EDCs modulate the expression of R-ras genes and thus affect subsequent signal transduction and tumor development.
Rhee
Jae-Sung
JS
Department of Molecular and Environmental Bioscience, Graduate School, Hanyang University, Seoul 133-791, South Korea.
Lee
Young-Mi
YM
Raisuddin
Sheikh
S
Lee
Jae-Seong
JS
D000595:Amino Acid Sequence; D000818:Animals; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000633:toxicity; D004965:Estrogen Antagonists / Q000633:toxicity; D005260:Female; D023781:Fundulidae / Q000196:embryology / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D011905:Genes, ras; D057850:Hermaphroditic Organisms; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D019849:Sex Determination Processes; D013629:Tamoxifen / Q000633:toxicity; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004958:Estradiol; D004965:Estrogen Antagonists; D010636:Phenols; D012333:RNA, Messenger; D013629:Tamoxifen; D014874:Water Pollutants, Chemical; D018631:ras Proteins; C041594:4-nonylphenol; C105260:4-tert-octylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds