Endocrine Abstracts

Background: There is considerable evidence to support a role for the GH/IGF-I axis in the development of breast cancer. We have previously demonstrated that IGF-I is expressed in both normal and malignant breast tissue, but that approximately 10% of primary breast cancers reveal no IGF-I mRNA expression. However the molecular differences between IGF-I positive and IGF-I negative tumours is unknown.

Aims: To investigate the molecular differences between IGF-I positive and IGF-I negative breast cancers using cRNA microarray analysis.

Methods: The IGF-I expression status of 76 primary breast cancers was identified using real-time RT-PCR ('Taqman'). Two IGF-I positive and two IGF-I negative breast tumours were subsequently selected and cRNA microarray analysis was performed using the Affymetrix U133A Chip protocol. The resultant data was analysed using Gene Spring 6.0 expression analysis software.

Results: 39 genes were upregulated (>2 fold) in the IGF-I positive tumours, compared to the IGF-I negative tumours. These included carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1), which was upregulated 3.35 fold. CEACAM1 exhibits marked angiogenic properties in vitro and in vivo. Transforming growth factor beta 1, a multifunctional peptide that controls proliferation and differentiation, was also upregulated 2.15 fold in the IGF-I positive tumours. In addition it has been shown to promote the formation of lung metastases in animal models of breast cancer. 23 genes were found to be downregulated (> 2 fold) in the IGF-1 positive tumours, including suppression of tumourigenicity 13. This is an abundant highly conserved protein that binds heat shock proteins and has previously been shown to be down regulated in breast, colorectal and ovarian carcinoma.

Conclusion: Expression of local IGF-I by breast cancers is accompanied by differential expression of numerous cancer-associated genes. Clarification of these genes will further elucidate the mechanisms by which IGF-I influences the pathogenesis of breast cancer.