Dataset Information

Distinct expression pattern and post-transcriptional regulation of cell cycle genes in the glandular epithelia of avian ovarian carcinomas.

ABSTRACT: The cell cycle system is controlled in a timely manner by three groups of cyclins, cyclin dependent kinases and cyclin dependent kinase inhibitors. Abnormal alterations of cell cycle regulatory mechanisms are a common feature of many diseases including numerous tumor types such as ovarian cancer. Although a variety of cell cycle regulatory genes are well known in mammalian species including human and mice, they are not well studied in avian species, especially in laying hens which are recognized as an excellent animal model for research relevant to human ovarian carcinogenesis. Therefore, in the present study, we focused on comparative expression and regulation of expression of candidate genes which might be involved in the cell cycle program in surface epithelial ovarian cancer in laying hens. Our current results indicate that expression levels of cell cycle gene transcripts are greater in cancerous as compared to normal ovaries. In particular, cyclin A2 (CCNA2), CCND1, CCND2, CCND3, CCNE2, cyclin dependent kinase 1 (CDK1), CDK3, CDK5, cyclin dependent kinases inhibitor 1A (CDKN1A) and CDKN1B were upregulated predominantly in the glandular epithelia of cancerous ovaries from laying hens. Further, several microRNAs (miRs), specifically miR-1798, miR-1699, miR-223 and miR-1744 were discovered to influence expression of CCND1, CCNE2, CDK1, and CDK3 mRNAs, respectively, via their 3'-UTR which suggests that post-transcriptional regulation of gene expression influences their expression in laying hens. Moreover, miR-1626 influenced CDKN1A expression and miR-222, miR-1787 and miR-1812 regulated CDKN1B expression via their 3'-UTR regions. Collectively, results of the present study demonstrate increased expression of cell cycle-related genes in cancerous ovaries of laying hens and indicate that expression of these genes is post-transcriptionally regulated by specific microRNAs.

SUBMITTER: Lee JY

PROVIDER: S-EPMC3517539 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Distinct expression pattern and post-transcriptional regulation of cell cycle genes in the glandular epithelia of avian ovarian carcinomas.

Lee Jin-Young JY Jeong Wooyoung W Kim Ji-Hye JH Kim Jinyoung J Bazer Fuller W FW Han Jae Yong JY Song Gwonhwa G

PloS one 20121207 12

The cell cycle system is controlled in a timely manner by three groups of cyclins, cyclin dependent kinases and cyclin dependent kinase inhibitors. Abnormal alterations of cell cycle regulatory mechanisms are a common feature of many diseases including numerous tumor types such as ovarian cancer. Although a variety of cell cycle regulatory genes are well known in mammalian species including human and mice, they are not well studied in avian species, especially in laying hens which are recognized ...[more]

PMID: 23236518

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Project description:BACKGROUND: It is known that all tumors studied in sufficient number to draw conclusions show characteristic/specific chromosomal rearrangements, and the identification of these chromosomes and the genes rearranged behind the aberrations may ultimately lead to a tailor-made therapy for each cancer patient. Knowledge about the acquired genomic aberrations of ovarian carcinomas is still unsatisfactory. METHODS: We cytogenetically analyzed 110 new cases of ovarian carcinoma of different histological subtypes using karyotyping of G-banded chromosomes and high-resolution comparative genomic hybridization. We first compared the aberration patterns identified by the two genomic screening techniques using the so-called "classical" pathological classification in which the carcinomas are grouped as tumors of types I and II. We also broke down our findings according to the more "modern" classification which groups the carcinomas in five different categories. RESULTS: The chromosomal breakpoints identified by karyotyping tended to cluster to 19p/q and to 11q, but no unquestionably recurrent rearrangement could be seen. Common imbalances were scored as gains from 1q, 3q, 7q, and 8q and losses from 17p, 19q, and 22q. Gain of material from 8q23 and losses from 19q and 22q have previously been described at high frequencies in bilateral and borderline ovarian carcinomas. The fact that they were present both in "precursor" lesions, i.e., borderline tumors, as well as in tumors of more advanced stages, i.e., carcinomas, highlights the possibility of an adenoma-carcinoma sequence in ovarian carcinogenesis. CONCLUSION: Based on the relatively simple genomic changes we identified in the low-grade serous carcinomas examined (n = 7) and which largely corresponded to the aberration pattern formerly identified in borderline tumors, one can interpret the cytogenetic data as supporting the view that the low-grade carcinomas represent a phenotypically more advanced stage of borderline tumors. Whether transition from low-grade to high-grade carcinoma also occurs, is a question about which the genomic data is still inconclusive.

Project description:Several studies described a role for the E2F/Rb pathway in ovarian serous carcinomas (SCAs). Since E2F/Rb pathway deregulation is a general hallmark of human cancer, it remains unclear whether this deregulation is of particular importance in SCAs or whether it reflects a common oncologic feature. Here, we attempted to clarify this issue by the examination of microarray expression profiles of SCAs (10 SCA1s, 15 SCA3s) and particularly by the comparison with another, less malignant, ovarian cancer type, serous borderline tumours (13 SBTs). Results were further validated by quantitative RT-PCR, both on the microarray samples and an independent panel. In addition, TP53 mutation analysis was performed. This integrated analysis revealed a significant increase in the expression of the transcription factors E2F1 and E2F3 in SCAs, when compared to SBTs. This was associated with a vast overexpression of E2F target genes in SCAs compared to SBTs. Overall, at least 45% of those genes with a significantly higher expression in SCAs were E2F targets. When taking into account the different SCA tumour grades, particularly SCA3s exhibited a major deregulated E2F target expression pattern, compared to SBTs. To a lesser extent, this was also the case for SCA1s, although the E2F target expression pattern of several SCA1s appeared to be more similar to SBTs. Generally, overexpression of E2F targets in SCAs appeared to be well-structured since those targets considered as negative regulators of the cell cycle or promoters of apoptosis were usually not overexpressed in SCAs. Similar to E2F target deregulation, TP53 mutations were identified in SCA3s, to a lesser extent in SCA1s, and not in SBTs. These results suggest that a structured, generally upregulated, E2F transcription factor activity is associated with a global cell cycle disturbance in high grade SCAs, and exceeds typical E2F/Rb pathway disruption in tumours, at least compared with SBTs Experiment Overall Design: Expression levels of 13 SBTs, including 2 micropapillary SBTs (MPCs), 10 SCAs grade 1 (SCA1s), and 15 SCAs grade 3 (SCA3s) were compared.

Dataset Information

Distinct expression pattern and post-transcriptional regulation of cell cycle genes in the glandular epithelia of avian ovarian carcinomas.

Publications

Distinct expression pattern and post-transcriptional regulation of cell cycle genes in the glandular epithelia of avian ovarian carcinomas.

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