Differential expression of claudin family proteins in mouse ovarian serous papillary epithelial adenoma in aging FSH receptor-deficient mutants.
Ovarian cancer is a deadly disease with long latency. To understand the consequences of loss of follicle-stimulating hormone receptor (FSH-R) signaling and to explore why the atrophic and anovulatory ovaries of follitropin receptor knockout (FORKO) mice develop different types of ovarian tumors, including serous papillary epithelial adenoma later in life, we used mRNA expression profiling to gain a comprehensive view of misregulated genes. Using real-time quantitative reverse transcription-polymerase chain reaction, protein analysis, and cellular localization, we show, for the first time, in vivo evidence that, in the absence of FSH-R signaling, claudin-3, claudin-4, and claudin-11 are selectively upregulated, whereas claudin-1 decreases in ovarian surface epithelium and tumors in comparison to wild type. In vitro experiments using a mouse ovarian surface epithelial cell line derived from wild-type females reveal direct hormonal influence on claudin proteins. Although recent studies suggest that cell junction proteins are differentially expressed in ovarian tumors in women, the etiology of such changes remains unclear. Our results suggest an altered hormonal environment resulting from FSH-R loss as a cause of early changes in tight junction proteins that predispose the ovary to late-onset tumors that occur with aging. More importantly, this study identifies claudin-11 overexpression in mouse ovarian serous cystadenoma.
Aravindakshan
Jayaprakash
J
Molecular Reproduction Research Laboratory, Clinical Research Institute of Montréal, Montreal, Quebec, Canada H2W 1R7.
Chen
Xinlei
X
Sairam
M Ram
MR
D000236:Adenoma / Q000235:genetics / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D002460:Cell Line; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D011962:Receptors, FSH / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; C568113:Cldn1 protein, mouse; C492354:Cldn11 protein, mouse; C568123:Cldn3 protein, mouse; C568158:Cldn4 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011962:Receptors, FSH