Expression of the H19 Oncofetal Gene in Premalignant Lesions of Cervical Cancer: A Potential Targeting Approach for Development of Nonsurgical Treatment of High-Risk Lesions

Tomer Feigenberg,Avraham Hochberg,Galina Pizov,Abraham Benshushan,Ofer N Gofrit

doi:10.1155/2013/137509

Tomer Feigenberg, Avraham Hochberg + Show 3 more

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https://doi.org/10.1155/2013/137509

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Abstract

Background. Recent data suggest a role for H19 gene in promoting cancer transformation and progression. Cervical cancer, progresses from high-grade lesions (CIN3). At present, it is unclear if CIN lesions express H19. Objectives. To determine H19 expression in patient samples of CIN3 as well as the ability of a construct in which the promoter from the H19 gene drives expression of the diphtheria toxin A chain (DTA) to inhibit cervical cancer cell growth in vitro. Methods. H19 transcript levels were evaluated on 10 biopsies of CIN3 using in situ hybridization. PCR was used to examine H19 expression in cervical cancer cell lines and in two samples from a patient with cervical carcinoma. Cell lines were transfected with H19-DTA to determine its impact on cell number. Results. H19 gene was expressed in the area of CIN3 in 9 out of 10 samples. RT-PCR indicated expression of H19 in cervical cancer samples and in one of the three cell lines examined. Transfection of all cell lines with H19-DTA vector resulted in inhibited cell growth. Conclusions. H19 is expressed in the majority of CIN3 samples. These results suggest that most CIN3 lesions could be targeted by H19-DTA. Further in vivo preclinical studies are thus warranted.

Highlights

Carcinoma of the uterine cervix is the second most common cancer worldwide
Since premalignant human-derived cell lines or valid animal models for premalignant cervical lesions are not currently available, we examined the ability of the H19-diphtheria toxin A chain (DTA) construct to inhibit cell growth of available cervical cancer cell lines
In Situ Hybridization (ISH) for H19 RNA was conducted as described in the Methods section

Summary

Introduction

Carcinoma of the uterine cervix is the second most common cancer worldwide. Every year, cervical cancer is diagnosed in about 500,000 women globally and is responsible for more than 280,000 deaths. Infection with HPV is diagnosed in as many as 99% of the women diagnosed with squamous cervical carcinoma cancer of the uterus. To determine H19 expression in patient samples of CIN3 as well as the ability of a construct in which the promoter from the H19 gene drives expression of the diphtheria toxin A chain (DTA) to inhibit cervical cancer cell growth in vitro. PCR was used to examine H19 expression in cervical cancer cell lines and in two samples from a patient with cervical carcinoma. RT-PCR indicated expression of H19 in cervical cancer samples and in one of the three cell lines examined. H19 is expressed in the majority of CIN3 samples These results suggest that most CIN3 lesions could be targeted by H19-DTA.

Objectives

Methods

Results

Conclusion