Overexpression of kallikrein 10 in epithelial ovarian carcinomas

Ovarian cancer is characterize by few early symptoms, presentation at an advanced stage, and poor survival. As a result, it is the most frequent cause of death from gynecological cancer. During the last decade, a research effort has been directed toward improving outcomes for ovarian cancer by screening for preclinical, early stage disease using both imaging techniques and serum markers. Numerous biomarkers have shown potential in samples from clinically diagnosed ovarian cancer patients, but few have been thoroughly assessed in preclinical disease and screening. The most thoroughly investigated biomarker in ovarian cancer screening is CA125. Prospective studies have demonstrated that both CA125 and transvaginal ultrasound can detect a significant proportion of preclinical ovarian cancers, and refinements in interpretation of results have improved sensitivity and reduced the false-positive rate of screening. There is preliminary evidence that screening can improve survival, but the impact of screening on mortality from ovarian cancer is still unclear. Prospective studies of screening are in progress in both the general population and high-risk population, including the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKC-TOCS), a randomized trial involving 200,000 postmenopausal women designed to document the impact of screening on mortality. Recent advances in technology for the study of the serum proteome offer exciting opportunities for the identification of novel biomarkers or patterns of markers that will have greater sensitivity and lead time for preclinical disease than CA125. Considerable interest and controversy has been generated by initial results utilizing surface-enhanced laser desorption/ionization (SELDI) in ovarian cancer. There are challenging issues related to the design of studies to evaluate SELDI and other proteomic technology, as well as the reproducibility, sensitivity, and specificity of this new technology. Large serum banks such as that assembled in UKCTOCS, which contain preclinical samples from patients who later developed ovarian cancer and other disorders, provide a unique resource for carefully designed studies of proteomic technology. There is a sound basis for optimism that further developments in serum proteomic analysis will provide powerful methods for screening in ovarian cancer and many other diseases.

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“…Preliminary reports indicate that two kallikreins (hK6 and hK10) may be useful serum biomarkers for diagnosis of ovarian (16)(17)(18).…”

Section: Ovx1mentioning

confidence: 99%

Progress and Challenges in Screening for Early Detection of Ovarian Cancer

Jacobs

Menon

2004

Molecular & Cellular Proteomics

416

312

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“…Furthermore, many microarray studies have tried to (85,86,88,89,(117)(118)(119)(120)(121)(122)(123)(124)(125)(126)(127)(128)(129)(130)(131)(132)(133)(134)(135) Carcinogenesis Carcinomas 3 (87,(136)(137)(138) Molecular determinants of classic clinicopathologic factors (stage, grade, histotype, (sub)optimal cytoreduction, response to chemotherapy)…”

Section: Dna Microarray Studies In Ovarian Cancermentioning

confidence: 99%

Molecular prognostic markers in ovarian cancer: toward patient-tailored therapy

Crijns

Duiker

Jong

et al. 2006

Int J Gynecol Cancer

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In ovarian cancer the ceiling seems to be reached with chemotherapeutic drugs. Therefore a paradigm shift is needed. Instead of treating all patients according to standard guidelines, individualized molecular targeted treatment should be aimed for. This means that molecular profiles of the distinct ovarian cancer subtypes should be established. Until recently, most studies trying to identify molecular targets were single-marker studies. The prognostic role of key components of apoptotic and prosurvival pathways such as p53, EGFR, and HER2 has been extensively studied because resistance to chemotherapy is often caused by failure of tumor cells to go into apoptosis. However, it is more than likely that different ovarian cancer subtypes with extensive molecular heterogeneity exist. Therefore, exploration of the potential of specific tumor-targeted therapy, based on expression of a prognostic tumor profile, may be of interest. Recently, new profiling techniques, such as DNA and protein microarrays, have enabled high-throughput screening of tumors. In this review an overview of the current status of prognostic marker and molecular targeting research in ovarian cancer, including microarray studies, is presented.

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“…The prognostic value of at least 11 out of 15 members of the human kallikrein family in ovarian cancer has been also published (Clements et al, 2004;Yousef et al, 2005;Prezas et al, 2006;Dorn et al, 2007). Six kallikreins, KLK4, KLK5, KLK6, KLK7, KLK10, and KLK15 (Kim et al, 2001;Kyriakopoulou et al, 2003;Shvartsman et al, 2003;Yousef et al, 2003c;Kountourakis et al, 2008), are markers of poor prognosis in ovarian cancer. Two kallikreins, KLK9 ) and KLK14 (Yousef et al, 2003a), are markers of favourable prognosis.…”

mentioning

confidence: 99%

“…The KLK10 protein was also purified from ascites fluid of ovarian cancer patients (Luo et al, 2006). Reports have shown diagnostic and prognostic uses of KLK10 in ovarian cancer (Shvartsman et al, 2003), and as such, it represents a possible therapeutic target for metastatic ovarian cancer.…”

mentioning

confidence: 99%

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

et al. 2010

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BACKGROUND: Kallikrein-related peptidases (KLKs) are a family of serine proteases that have been shown to be dysregulated in several malignancies including ovarian cancer. The control of kallikrein genes and their physiological function in cancer is not well understood. We hypothesized that microRNAs (miRNAs) represent a novel mechanism for post-transcriptional control of KLK expression in cancer. METHODS: We first analysed miRNA expression in ovarian cancer in silico. A total of 98 miRNAs were reported to have altered expression in ovarian cancer. Three of these miRNAs were predicted to target KLK10. We experimentally verified the predicted miR -KLK10 interaction using two independent techniques, a luciferase assay with a construct containing the KLK10 3 0 untranslated region (UTR), pMIR -KLK10, and measuring KLK10 protein levels after transfection with miRNA. RESULTS: When we co-transfected cells with pMIR -KLK10 and either let-7f, miR-224, or mR-516a, we saw decreased luciferase signal, suggesting that these miRNAs can target KLK10. We then examined the effect of these three miRNAs on KLK10 protein expression and cell growth. Transfection of all miRNAs, let-7f, miR-224, and miR-516a led to a decrease in protein expression and cellular growth. This effect was shown to be dose dependent. The KLK10 protein levels were partially restored by co-transfecting let-7f and its inhibitor. In addition, there was a slight decrease in KLK10 mRNA expression after transfection with let-7f. CONCLUSIONS: Our results confirm that KLKs can be targeted by more than one miRNA. Increased expression of certain miRNAs in ovarian cancer can lead to decreased KLK protein expression and subsequently have a negative effect on cell proliferation. This dose-dependent effect suggests that a 'tweaking' or 'fine-tuning' mechanism exists in which the expression of one KLK can be controlled by multiple miRNAs. These data together suggest that miRNA may be used as potential therapeutic options and further studies are required.

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Overexpression of kallikrein 10 in epithelial ovarian carcinomas

Cited by 64 publications

References 20 publications

Progress and Challenges in Screening for Early Detection of Ovarian Cancer

Progress and Challenges in Screening for Early Detection of Ovarian Cancer

Molecular prognostic markers in ovarian cancer: toward patient-tailored therapy

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

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