Expression of cyclin D1 correlates with malignancy in human ovarian tumours

Barbieri, Federica; Cagnoli, Monica; Ragni, Nicola; Pedullà, F.; Foglia, G.; Alama, Angela

doi:10.1038/bjc.1997.215

Cited by 35 publications

(25 citation statements)

References 17 publications

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“…This is also evident from the cell cycle of SKOV3 cells; WFDC2 gene silencing arrested the cell cycle in the G0/G1 phase. Cyclin D1 belongs to the core cell cycle machinery and it is frequently overexpressed in human cancers (13,24,25). The strong positive correlation between WFDC2 and cyclin D1 expression observed in our study suggests that WFDC2 may be linked to the development and progression of ovarian cancer by regulating the cell cycle of ovarian cancer cells.…”

Section: Discussionsupporting

confidence: 57%

WAP four-disulfide core domain protein 2 mediates the proliferation of human ovarian cancer cells through the regulation of growth- and apoptosis-associated genes

Yao

Wang

et al. 2012

Oncology Reports

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Abstract. The WAP four-disulfide core domain protein 2 (WFDC2) is frequently overexpressed in epithelial ovarian cancer cells and has been proposed as a potential biomarker. The biological function of WFDC2 in tumor progression remains unclear. In this study, the stable expression of short hairpin RNA (shRNA) against WFDC2 in the human ovarian SKOV3 cell line was established. Cell proliferation in vitro was determined by MTT assay. Cell cycle and apoptosis were analyzed by FACS. The expression of genes related to cell proliferation and survival was detected by real-time RT-PCR and western blotting. In vivo tumor growth assay was performed by establishing WFDC2-knockdown xenografts in nude mice and monitoring tumor growth. The expression of WFDC2, Ki67 and activated caspase-3 was analyzed by immunohistochemistry in order to determine the role of WFDC2 in proliferation and apoptosis. Our results revealed that the silencing of WFDC2 abolished ovarian cancer cell proliferation, suppressing tumor formation and growth in ovarian cancer cells both in vitro and in vivo. The knockdown of WFDC2 induced upregulation of Fasl and the downregulation of cyclin D1 activated caspase-3 and Ki67. These results indicate that WFDC2 plays a crucial role in tumor formation and growth in ovarian cancer cells. WFDC2 may be a potential therapeutic target for epithelial ovarian cancer. IntroductionOvarian cancer is one of the most common cancers among women, and it is the leading cause of mortality among gynecological malignancies worldwide. WAP four-disulfide core domain protein 2 (WFDC2) was first identified in the epithelium of the distal epididymis and was originally predicted as a protease inhibitor involved in sperm maturation. Recent interest in WFDC2 has been generated by the consistent demonstration of its overexpression in ovarian carcinomas in comparison to normal ovarian tissue (1-3). This gene, also known as human epididymis 4 (HE4), has been consistently identified as being upregulated in ovarian carcinoma by gene expression profiling studies and has been proposed as a putative serum biomarker for malignant ovarian masses (1,4-6).The WFDC2 gene is located on human chromosome 20q12-13.1. The amplification of 20q12-13 has been demonstrated specifically in breast and ovarian carcinomas (2,7). Fourteen genes which encode proteins with a WAP-type four-disulfide core (WFDC) domain have been identified on this region. Two of these genes, SLPI and p13, encoded as antileukoproteinase 1 and elafin, which are co-expressed with WFDC2 play a role in the development or progression of various types of carcinomas (8,9). This led us to investigate whether WFDC2, a member of the WAP cluster, overexpressed in ovarian cancer, may also be involved with this disease.The most studied WAP proteins, p13 and SLPI, both identified as serine-proteinase inhibitors, are reported to be associated with aggressive, high-risk, or metastatic cancer originating from various organs (10,11). The expression of SLPI was positively correlated with the increased exp...

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Section: Discussionsupporting

confidence: 57%

WAP four-disulfide core domain protein 2 mediates the proliferation of human ovarian cancer cells through the regulation of growth- and apoptosis-associated genes

Yao

Wang

et al. 2012

Oncology Reports

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“…Recently using Western analysis, cyclin D1 protein was detected in 90% of the malignant ovarian tumours examined (Barbieri et al, 1997). The high level of cyclin D1 overexpression in this study compared with previous findings (Hung et al, 1996;Worsley et al, 1997) may reflect differences in sensitivity of detection of Western blotting compared with IHC.…”

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confidence: 47%

“…Clearly, there is a need for a greater understanding of the mechanisms involved in disease pathogenesis to allow development of preventive strategies as well as prognostic markers that could be used in patient management. Recent studies using Western analysis have shown that cyclin D1 is overexpressed in the majority of malignant ovarian tumours but is absent in benign lesions (Barbieri et al, 1997). In this analysis the subcellular localization of cyclin D1 was not determined.…”

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confidence: 87%

Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells

Dhar

Branigan

Parkes³

et al. 1999

Br J Cancer

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SummaryThe expression of cyclin D1 protein in tumour sections from 81 patients with epithelial ovarian cancer was analysed using immunohistochemistry. The tumours that overexpressed cyclin D1 in more than 10% of neoplastic cells were considered positive. Thus overexpression of cyclin D1 was observed in 72/81 (89%) of the cases examined. Protein was detected in both the nucleus and the cytoplasm in 24/81 (30%) and localized exclusively in the cytoplasm in 48/81 (59%) of the tumours. Cyclin D1 was overexpressed in both borderline and invasive tumours. There was no association between protein overexpression and tumour stage and differentiation. Furthermore, no correlation between cyclin D1 expression and clinical outcome was observed. However, in tumours overexpressing cyclin D1 (n = 72), the proportion displaying exclusively cytoplasmic localization of protein was higher in those with serous compared with non-serous histology (P = 0.004, odds ratio 4.8, 95% confidence interval 1.4-19.1). Western analysis using a monoclonal antibody to cyclin D1 identified a 36 kDa protein in homogenates from seven tumours displaying cytoplasmic only and one tumour demonstrating both nuclear and cytoplasmic immunostaining. Using restriction fragment length polymorphism polymerase chain reaction and PCR-multiplex analysis, amplification of the cyclin D1 gene (CCNDI) was detected in 1/29 of the tumours demonstrating overexpression of cyclin D1 protein. We conclude that deregulation of CCND1 expression leading to both cytoplasmic and nuclear protein localization is a frequent event in ovarian cancer and occurs mainly in the absence of gene amplification.

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“…In tumour cells, the ability of Rb to bind transcription factors is disrupted and the checkpoint is eliminated. In retinoblastoma, small cell lung carcinomas, and in many sarcomas and bladder carcinomas, pRB function is lost through mutations of the pRB gene (Horowitz et al 1990 Cyclin D1 is a G 1 -specific protein essential for the progression from G 1 phase to S phase; its expression and activity reach a peak in G 1 and gradually decline in S phase (Barbieri et al 1997). Cyclin D1 plays a pivotal role in the regulation of progression from the G 1 to the S phase of the cell cycle through the formation of active enzyme complexes with cyclin-dependent kinases Cdk4 and Cdk6.…”

Section: Discussionmentioning

confidence: 99%

Pathological and immunohistochemical studies on rare cases of primary extragenital transmissible venereal tumours in the mammary gland

Gupta¹,

Sood²

2012

Vet. Med. - Czech

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Transmissible venereal tumours (TVT) are normally seen on the genitalia of both male and female dogs, and at times may be observed on extra-genital sites such as lips, oral mucosa, and peritoneum, or in organs such as the tonsils, eye, liver, spleen, kidney, lung, and musculature. The present communication deals with two rare cases of primary extragenital TVT involving the mammary glands of dogs and their pathology and immunohistochemistry. The study indicated that apart from routinely used markers such as vimentin, p53, PCNA, Ki-67 and c-myc, the oncogenes Rb and cyclin D1 proved to be novel markers of TVT in dogs. To the authors' knowledge, this is the first report of extra-genital mammary TVT in canines.

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Expression of cyclin D1 correlates with malignancy in human ovarian tumours

Cited by 35 publications

References 17 publications

WAP four-disulfide core domain protein 2 mediates the proliferation of human ovarian cancer cells through the regulation of growth- and apoptosis-associated genes

WAP four-disulfide core domain protein 2 mediates the proliferation of human ovarian cancer cells through the regulation of growth- and apoptosis-associated genes

Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells

Pathological and immunohistochemical studies on rare cases of primary extragenital transmissible venereal tumours in the mammary gland

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