FSH-regulated gene expression profiles in ovarian tumours and normal ovaries.
Development, growth and function of the ovary are controlled by endocrine and paracrine signals. These may also influence the development of ovarian cancer. The aim of this study was to identify the key molecular markers of the unregulated growth and hormone synthesis seen in ovarian tumours, particularly in granulosa cell tumours (GCT). Genes used in this study were chosen on the basis of our understanding of growth and differentiation in the normal ovary. We sought to define the patterns of gene expression in a panel of epithelial and stromal ovarian tumours. Expression was determined by RT-PCR using gene-specific primers for the FSH receptor (FSHR); the FSH early response genes: regulatory subunit of protein kinase A (RII-beta), cyclin D2 (cycD2) and sgk; and late response markers: cyclooxygenase-2 (COX-2) and the LH receptor (LHR). The GCT had high expression of FSHR compared with normal ovaries and the other tumours. cycD2 and RII-beta and COX-2 genes were also highly expressed in the GCT. sgk and LHR expression was lower in all of the tumours than in normal ovaries. Serous cystadenocarcinomas also had an unexpectedly high expression of COX-2. Comparison of the gene expression profiles between each tumour group suggests a molecular phenotype for GCT that is similar to that reported for FSH stimulated pre-ovulatory granulosa cells.
Chu
S
S
Prince Henry's Institute of Medical Research and the Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, 3168, Australia.
Rushdi
S
S
Zumpe
E T
ET
Mamers
P
P
Healy
D L
DL
Jobling
T
T
Burger
H G
HG
Fuller
P J
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D003536:Cystadenocarcinoma / Q000235:genetics* / Q000378:metabolism; D018282:Cystadenocarcinoma, Mucinous / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006106:Granulosa Cell Tumor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins; D008875:Middle Aged; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D010053:Ovary / Q000502:physiology*; D017697:Premenopause; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism; D012016:Reference Values; D000099184:Serum-Glucocorticoid Regulated Kinases
D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D017868:Cyclic AMP-Dependent Protein Kinases; D056742:Cyclin D2; D016213:Cyclins; D005640:Follicle Stimulating Hormone; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011962:Receptors, FSH; D011974:Receptors, LH; D000099184:Serum-Glucocorticoid Regulated Kinases; C080336:CCND2 protein, human; C517837:PRKAR2B protein, human