PMC42, a breast progenitor cancer cell line, has normal-like mRNA and microRNA transcriptomes

Anna Git^*¹ , Inmaculada Spiteri^*¹ , Cherie Blenkiron¹ , Mark J Dunning¹ , Jessica CM Pole² , Suet-Feung Chin¹ , Yanzhong Wang¹^,3 , James Smith⁴ , Frederick J Livesey⁴ and Carlos Caldas¹

¹Breast Cancer Functional Genomics Laboratory, Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK

²Department of Pathology, Hutchison-MRC Research Centre, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK

³Current address: Robertson Centre for Biostatistics, Boyd Orr Building, University of Glasgow, Glasgow G12 8QQ, UK

⁴Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK

author email corresponding author email* Contributed equally

Breast Cancer Research 2008, 10:R54doi:10.1186/bcr2109


Published:	27 June 2008

Abstract

Introduction

The use of cultured cell lines as model systems for normal tissue is limited by the molecular alterations accompanying the immortalisation process, including changes in the mRNA and microRNA (miRNA) repertoire. Therefore, identification of cell lines with normal-like expression profiles is of paramount importance in studies of normal gene regulation.

Methods

The mRNA and miRNA expression profiles of several breast cell lines of cancerous or normal origin were measured using printed slide arrays, Luminex bead arrays, and real-time reverse transcription-polymerase chain reaction.

Results

We demonstrate that the mRNA expression profiles of two breast cell lines are similar to that of normal breast tissue: HB4a, immortalised normal breast epithelium, and PMC42, a breast cancer cell line that retains progenitor pluripotency allowing in-culture differentiation to both secretory and myoepithelial fates. In contrast, only PMC42 exhibits a normal-like miRNA expression profile. We identified a group of miRNAs that are highly expressed in normal breast tissue and PMC42 but are lost in all other cancerous and normal-origin breast cell lines and observed a similar loss in immortalised lymphoblastoid cell lines compared with healthy uncultured B cells. Moreover, like tumour suppressor genes, these miRNAs are lost in a variety of tumours. We show that the mechanism leading to the loss of these miRNAs in breast cancer cell lines has genomic, transcriptional, and post-transcriptional components.

Conclusion

We propose that, despite its neoplastic origin, PMC42 is an excellent molecular model for normal breast epithelium, providing a unique tool to study breast differentiation and the function of key miRNAs that are typically lost in cancer.