Abstract

Ovarian cancer (OC) is characterized by a high morbidity and mortality, highlighting a great need for a better understanding of biological mechanisms that affect OC progression and improving its early detection methods. This study investigates effects of prolactin (PRL) on ovarian cancer cells, analyzes PRL receptors (PRLR) in tissue micro arrays and relates PRLR expression to survival of ovarian cancer. A database, composed of transcript profiles from OC, was searched for PRLR expression and results were put in relation to survival. Expression of PRLR in OC tissue sections and OC cell lines SKOV3, OV2008 and OVSAHO was assessed using immunohistochemistry, western blots and quantitative real-time PCR. The biological function of PRLR was evaluated by proliferation, colony formation and wound healing assays. Levels of PRLR mRNA are related to survival; in epithelial OC a high PRLR mRNA expression is related to a shorter survival. Analysis of a tissue micro array consisting of 84 OC showed that 72% were positive for PRLR immuno-staining. PRLR staining tended to be higher in OC of high grade tumors compared to lower grades. PRLR mRNA and protein can further be detected in OC cell lines. Moreover, in vitro treatment with PRL significantly activated the JAK/STAT pathway. PRLR expression is associated with OC survivals. PRL and its receptor may play an onco-modulatory role and promote tumor aggressiveness in OC. Alternatively, increased PRLR levels may form a base for the development of PRLR antagonist or PRLR antagonist-drug conjugate to increase selective uptake of anti-cancer drugs.

Highlights

  • Ovarian cancer (OC) is often diagnosed at an advanced stage and is a major cause of morbidity and mortality in women worldwide with higher mortality compared to other gynecologic malignancies [1, 2]

  • Data base searches were conducted using the search term prolactin receptor (PRLR), jetset selects the optimal probe set for PRL receptors (PRLR) gene using a scoring method established to assess each probe set for specificity, coverage and degradation resistance

  • Increased PRLR expression associated with short survivals in OC patients Different PRLR markers of OC prognosis have been identified using literature search

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Summary

Introduction

Ovarian cancer (OC) is often diagnosed at an advanced stage and is a major cause of morbidity and mortality in women worldwide with higher mortality compared to other gynecologic malignancies [1, 2]. Most of OC cases are diagnosed in advanced stages due to a high invasive nature, lack of early symptoms, screening strategies and diagnostic markers. Trans-vaginal ultrasound and serum measurement of serum cancer antigen 125 (CA-125) are currently used as a screening test for the high-risk population. These screening modalities lacks selectivity toward malignant and benign tumors [8]. Other novel biomarkers for OC have not yet fulfilled criteria of sensitivity and specificity to be approved for clinical application [12]

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