Endocrine Abstracts (2004) 7 P102

IGF-I and IGFBP-3 mRNA expression in tamoxifen-resistant, recurrent breast cancers

K McCarthy1, CA Laban1, CJ McVittie1, WB Ogunkolade2, S Khalaf3, SA Bustin2, R Carpenter1 & PJ Jenkins3


1Department of Breast Surgery, Barts and The London, Queen Mary School of Medicine, London, UK; 2Department of Academic Surgery, Barts and The London, Queen Mary College, London, UK; 3Department of Endocrinology, Barts and The London Queen Mary School of Medicine, London, UK.


Introduction

Increased cross talk between the IGF-I and oestrogen signalling pathways has been implicated in the development of tamoxifen resistance in breast cancers. We have previously demonstrated IGF-I mRNA to be down-regulated in primary breast cancers. However, the expression of IGF-I and IGFBP-3 in recurrent, tamoxifen-resistant tumours is unknown.

Methods

Total RNA was extracted from 38 paired samples of primary breast cancers (T) and adjacent normal (N) tissue and from 13 recurrent tumours, resistant to tamoxifen (RT). Local Ethical Committee approval was obtained for the study. IGF-I and IGFBP-3 mRNA levels were quantified using real time RT-PCR ('Taqman') and expressed as log copy number per microgram total RNA.

Results

IGF-I mRNA was expressed by 32 (84%) of 38 T and 10 (77%) of 13 RT. There was no significant difference in IGF-I mRNA expression between T and AN when IGF-I negative samples were discounted (median copy number 1.28 x 10-7 versus 1.26 x 10-7). There was, however, a significant down regulation of IGF-I mRNA in the RT when compared to either their AN (median copy number 2.1 x 10-6 versus 2.8 x 10-7, p=0.008) or T (median copy number 2.1 x 10-6 versus 1.28 x 10-7, p=0.0001). IGFBP-3 mRNA was expressed by all samples [median copy numbers: 1.69 x 10-8 (AN), 1.49 x 10-8 (T) and 1.15 x 10-8 (RT)].

Discussion

The significant down regulation of IGF-I mRNA in tamoxifen treated, recurrent breast cancers might reflect the known inhibition of IGF-I by tamoxifen and suggests that up-regulation of IGF-I expression is not a feature in the development of tamoxifen resistance. The pathophysiological significance of the high level of expression of IGFBP-3 remains currently unknown.

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