Human Molecular Genetics, 2002, Vol. 11, No. 12 1449-1453
© 2002 Oxford University Press
Promoter switch: a novel mechanism causing biallelic PEG1/MEST expression in invasive breast cancer
1Department of Pathology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland, 2Department of Histopathology and 3Department of Surgery, Mater Hospital, Dublin 7, Ireland and 4Molecular Medicine Unit, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK
Received February 11, 2002; Accepted March 27, 2002
We have previously reported on the biallelic expression of the imprinted PEG1/MEST gene in infiltrating carcinomas of the breast. Putative loss of imprinting (LOI) of PEG1/MEST has subsequently also been implicated in the aetiology of lung adenocarcinomas and colon cancer. Taking advantage of our previous study, identifying seven infiltrating carcinomas of the breast, displaying biallelic PEG1/MEST expression, we have analysed the allelic usage of the two alternative PEG1/MEST transcripts encoding isoforms 1 and 2, separately. In addition, expression levels of the two transcripts have been measured by real-time RT–PCR, in order to elucidate the mechanism behind the switch from monoallelic transcription in normal breast tissue to biallelic expression in invasive cancer. The isoform 1 transcript is imprinted in both the paired normal tissue and the breast carcinomas. In contrast, the isoform 2 transcript is biallelically expressed, or in one case expressed from the opposite allele to isoform 1, raising the possibility that isoform 2 is polymorphically imprinted in normal breast tissue. In all the paired normal samples, isoform 1 is predominantly expressed, explaining the monoallelic profiles of these samples. However, in four of the seven biallelic carcinomas, isoform 2 is expressed at higher levels than isoform 1, indicating that a switch in expression from isoform 1 to isoform 2 is responsible for the biallelic profiles in these samples. Our results not only suggest a novel mechanism leading to biallelic expression detected when analysing the common 3'-UTR of the PEG1/MEST transcriptional unit, they are also indicative of the existence of further alternative PEG1/MEST transcripts.
* To whom correspondence should be addressed. Tel: +353 1 7162811; Fax: +353 1 2692016; Email: amanda.mccann{at}ucd.ie
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Sathyan, H. B. Golden, and R. C. Miranda Competing Interactions between Micro-RNAs Determine Neural Progenitor Survival and Proliferation after Ethanol Exposure: Evidence from an Ex Vivo Model of the Fetal Cerebral Cortical Neuroepithelium J. Neurosci., August 8, 2007; 27(32): 8546 - 8557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Valleley, S. F. Cordery, and D. T. Bonthron Tissue-specific imprinting of the ZAC/PLAGL1 tumour suppressor gene results from variable utilization of monoallelic and biallelic promoters Hum. Mol. Genet., April 15, 2007; 16(8): 972 - 981. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hikichi, T. Kohda, T. Kaneko-Ishino, and F. Ishino Imprinting regulation of the murine Meg1/Grb10 and human GRB10 genes; roles of brain-specific promoters and mouse-specific CTCF-binding sites Nucleic Acids Res., March 1, 2003; 31(5): 1398 - 1406. [Abstract] [Full Text] [PDF]
|
|