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.
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.
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)].
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.
22 - 24 Mar 2004
British Endocrine Societies