Research article

Identification of differentially expressed sense and antisense transcript pairs in breast epithelial tissues

Anita Grigoriadis^1,5 , Gavin R Oliver² , Austin Tanney² , Howard Kendrick³ , Matt J Smalley , Parmjit Jat⁴ and A Munro Neville¹

¹  Ludwig Institute for Cancer Research, 605 Third Avenue, New York, NY 10158, USA

²  Almac Diagnostics, 19 Seagoe Industrial Estate, Craigavon, Northern Ireland, BT63 5QD, UK

³  The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK

⁴  Department of Neurodegenerative Disease, Institute of Neurology, London, WC1N 3BG, UK

⁵  Breakthrough Breast Cancer Research Unit, Guy's Hospital, King's Health Partners AHSC, London, UK

author email corresponding author email

BMC Genomics 2009, 10:324doi:10.1186/1471-2164-10-324

Published:	17 July 2009

Abstract

Background

More than 20% of human transcripts have naturally occurring antisense products (or natural antisense transcripts – NATs), some of which may play a key role in a range of human diseases. To date, several databases of in silico defined human sense-antisense (SAS) pairs have appeared, however no study has focused on differential expression of SAS pairs in breast tissue. We therefore investigated the expression levels of sense and antisense transcripts in normal and malignant human breast epithelia using the Affymetrix HG-U133 Plus 2.0 and Almac Diagnostics Breast Cancer DSA microarray technologies as well as massively parallel signature sequencing (MPSS) data.

Results

The expression of more than 2500 antisense transcripts were detected in normal breast duct luminal cells and in primary breast tumors substantially enriched for their epithelial cell content by DSA microarray. Expression of 431 NATs were confirmed by either of the other two technologies. A corresponding sense transcript could be identified on DSA for 257 antisense transcripts. Of these SAS pairs, 163 have not been previously reported. A positive correlation of differential expression between normal and malignant breast samples was observed for most SAS pairs. Orientation specific RT-QPCR of selected SAS pairs validated their expression in several breast cancer cell lines and solid breast tumours.

Conclusion

Disease-focused and antisense enriched microarray platforms (such as Breast Cancer DSA) confirm the assumption that antisense transcription in the human breast is more prevalent than previously anticipated. Expression of a proportion of these NATs has already been confirmed by other technologies while the true existence of the remaining ones has to be validated. Nevertheless, future studies will reveal whether the relative abundances of antisense and sense transcripts have regulatory influences on the translation of these mRNAs.