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Journal of Cancer Research and Clinical Oncology

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01.02.2011 | Original Paper

Regulation of IGF2 transcript and protein expression by altered methylation in breast cancer

verfasst von: Preetha J. Shetty, Sireesha Movva, Nagarjuna Pasupuleti, Bhavani Vedicherlla, Kiran K. Vattam, Sambasivan Venkatasubramanian, Yog R. Ahuja, Qurratulain Hasan

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2011

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Abstract

Purpose

Breast Cancer is one of the leading causes of cancer deaths among women worldwide. The role of epigenetics as a distinct mechanism to alter gene expression in a tissue-specific manner has emerged as an important mechanism in the pathophysiology of cancer. Present study was carried out to assess the role of methylation in regulating transcription and protein expression of Insulin-like growth factor 2 (IGF2), an oncogene with parental imprinting.

Methods

Paraffin-embedded archival breast tumor and adjacent normal tissue samples were used for carrying out PCR-based methylation assay, genomic PCR, immunohistochemistry and Real-Time Reverse transcriptase PCR.

Results

A significant loss of methylation in exon 9 CpG cluster of IGF2 in breast tumor tissues was observed when compared to normal tissue (P < 0.0001). Expression of IGF2 by immunohistochemistry exhibited a mean twofold increase correlating with the hypomethylation of this specific CpG. Real-Time RT PCR showed increased transcripts in the tumor tissue supporting the IHC and methylation results. A total of 33% of tumor samples heterozygous for the ApaI IGF2 polymorphism exhibited biallelic IGF2 expression due to loss of imprinting; this was not seen in any of the normal breast tissues.

Conclusions

Altered methylation of exonic CpG plays an important role in the enhanced transcription/expression of IGF2 in breast tumors. Methylation analysis of exon 9 CpG can be used as a biomarker for upregulation of IGF2 in breast tumor tissue and maybe developed as a diagnostic test in future.

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Titel: Regulation of IGF2 transcript and protein expression by altered methylation in breast cancer
verfasst von: Preetha J. Shetty
Sireesha Movva
Nagarjuna Pasupuleti
Bhavani Vedicherlla
Kiran K. Vattam
Sambasivan Venkatasubramanian
Yog R. Ahuja
Qurratulain Hasan
Publikationsdatum: 01.02.2011
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2011
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-010-0890-z

Springer Medizin

Regulation of IGF2 transcript and protein expression by altered methylation in breast cancer