Avian SERPINB11 gene: a marker for ovarian endometrioid cancer in chickens

Abstract

As serine and cysteine proteinase inhibitors, serpins, such as SERPINB5, cause ovarian, colorectal and pancreatic adenocarcinomas. We identified SERPINB11 as a novel estrogen-induced gene in chickens during oviduct development. The chicken is a unique animal model for research on human ovarian cancer, because it spontaneously develops epithelial cell-derived ovarian cancer as in women. Therefore, this study investigated the expression pattern, CpG methylation status, and miRNA regulation of the SERPINB11 gene in normal and cancerous ovaries from chickens. Our results indicate that SERPINB11 is most abundant in the glandular epithelium of endometrioid adenocarcinoma of cancerous, but not normal, ovaries of hens. In addition, bisulfite sequencing revealed that about 30% of -110 CpG sites are methylated in ovarian cancer cells, whereas -110 CpG sites are demethylated in normal ovarian cells. Next, we determined whether miR-1582 influences SERPINB11 expression via its 3'UTR and found that it does not directly target the 3'UTR of SERPINB11 mRNA. Therefore, it is unlikely that post-transcriptional regulation influences SERPINB11 expression in the chicken ovary. On the other hand, in human ovarian cancer cells such as OVCAR-3, SKOV-3 and PA-1 cells, immunoreactive SERPINB11 protein was predominant in the cytoplasm and had a similar expression pattern to that in chicken ovarian cancer cells. Collectively, these results suggest that SERPINB11 is a biomarker for chicken ovarian endometrioid carcinoma that could be used for diagnosis and monitoring effects of therapies for the disease in women.

Differential expression of vitelline membrane outer layer protein 1: Hormonal regulation of expression in the oviduct and in ovarian carcinomas from laying hens

“…The asterisks denote statistically significant differences (**P < 0.01, ***P < 0.001). et al, 2012a) and SERPINB11 (Lim et al, 2012b) that are crucial regulators of oviduct development in hens were also expressed predominantly in GE of cancerous ovaries from laying hens, and they were co-localized in chicken and human ovarian cancer cell lines.…”

“…We have examined the tumor stage in 10 hens with cancerous ovaries according to characteristic features of chicken ovarian cancer. (Barua et al, 2009;Lim et al, 2012b).…”

Prostaglandin D2 synthase related to estrogen in the female reproductive tract

“…Interestingly, the merits of the laying hen model are being recognized because mechanisms for progression of EOC and histological/pathological features are similar to EOC in women [12,31,32]. Indeed, we have reported several estrogen-stimulated genes that are expressed in GE of ovarian adenocarcinomas, but not normal ovaries from laying hens and these include cathepsin B (CTSB) [33], serpin peptidase inhibitor, clade B, member 11 (SERPINB11) [13], betadefensin 11 (AvBD-11) [34], and several cell cycle genes [35]. Although Fujimori and colleagues detected PTGDS expression in the ovaries of 24-week-old chickens [23], ovarian carcinoma generally occurs in laying hens that are 4-to 5-years of age.…”

“…As a control, normal (n = 5) ovaries were also collected from egglaying hens. We examined the tumor stage in 10 hens with using characteristic features of chicken ovarian cancer [12,13].…”

Diethylstilbestrol regulates expression of avian apolipoprotein D during regression and recrudescence of the oviduct and epithelial-derived ovarian carcinogenesis

“…Moreover, an alternative theory for the origin of ovarian cancer has recently proposed that the source of ovarian cancer cells is the oviduct [37,38]. Indeed, about 40% of the up-regulated genes in EOC of laying hens include serpin peptidase inhibitor, clade B, member 3 (SERPINB3) [39], SERPINB11 [40], SERPINB12 [41], alpha 2 macroglobulin (A2M) [42], S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) [43], pleiotrophin (PTN) [17], beta-defensin 11 (AvBD-11) [44], beta-catenin (CTNNB1) [45], prostaglandin D2 synthase (PTGDS2) [46], and vitelline membrane outer layer protein 1 (VMO1) [47] which are abundantly expressed during development and differentiation of the oviduct. In the present study, APOD mRNA and protein were abundantly and specifically detected in the GE of cancerous, but not normal ovaries of laying hens.…”