Inflammation-associated gene expression is altered between normal human ovarian surface epithelial cells and cell lines derived from ovarian adenocarcinomas.
Ovulation is believed to contribute to the development of ovarian cancers that derive from the ovarian surface epithelium (OSE). The process of ovulation is synonymous with inflammation and inflammatory cytokines such as interleukin-1alpha (IL-1alpha) have recently been shown to induce both inflammatory and anti-inflammatory responses in human OSE (HOSE) cells. In this study we directly compared levels of IL-1alpha-induced gene expression by analysing the levels of 11beta-hydroxysteroid dehydrogenase (11betaHSD) types 1 (11betaHSD-1) and 2 (11betaHSD-2), cyclooxygenase-2 (COX-2), IL-1 receptor (IL-1R) and glucocorticoid receptor alpha (GRalpha) mRNA between normal HOSE cells and cell lines derived from poorly differentiated (SKOV-3, BG-1, PEO-4) and well-differentiated (PEO-14) ovarian adenocarcinoma. In HOSE cell cultures, and to a lesser extent PEO-14 cells, the basal mRNA levels of COX-2 and 11betaHSD-1 were relatively high and further shown to be induced in response to IL-1alpha (for HOSE cells; >20-fold, P<0.05 and PEO-14 cells; >3fold, P<0.05). However, whereas HOSE cells expressed a low level of 11betaHSD-2 mRNA that was only mildly responsive to IL-1alpha (1.3-fold, P<0.001), all cell lines exhibited a higher basal level of 11betaHSD-2 mRNA that was in some cases further stimulated in PEO-4 cells (five-fold; P<0.05) or suppressed in SKOV-3 cells (two-fold; P<0.01) in response to IL-1alpha. All cells tested expressed IL-1R and, with the exception of BG-1, GRalpha. These results indicate that cell lines derived from ovarian cancers have lost the ability to respond normally to inflammatory cytokines such as IL-1alpha. The finding that normal OSE cells, in contrast to cell lines derived from patients with ovarian adenocarcinoma, abundantly express 11betaHSD-1 mRNA but are essentially devoid of 11betaHSD-2 mRNA supports the concept that the pattern of 11betaHSD isoform gene expression is a defining feature of neoplastic cellular transformation, which might have particular relevance to the ovary.
Gubbay
O
O
Centre for Reproductive Biology, The Chancellor's Building, University of Edinburgh, 49 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SB, UK. ogubby@staffmail.ed.ac.uk
Guo
W
W
Rae
M T
MT
Niven
D
D
Langdon
S P
SP
Hillier
S G
SG
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis; D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology*; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics*; D004847:Epithelial Cells; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000494:pharmacology; D008565:Membrane Proteins; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000276:immunology*; D010060:Ovulation; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D007375:Interleukin-1; D008565:Membrane Proteins; D042842:11-beta-Hydroxysteroid Dehydrogenases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases