Endocrine Abstracts

Background: The growth hormone/ insulin-like growth factor-1 (GH/IGF-1) axis has been increasingly implicated in the pathogenesis of breast cancer. We have recently demonstrated the local expression of both GH and IGF-I in normal and malignant breast tissue. However, the regulation of this local GH/IGF-1 expression is unknown. Aims: (i) To quantify the mRNA levels of GHRH, ghrelin and their receptors in malignant and adjacent normal breast tissue, and (ii) to determine any correlation between such expression and that of the tumour associated genes, PCNA, c-myc, Cox-2 and VEGF-189. Methods: Total RNA was extracted from 60 samples of paired normal breast epithelium and carcinoma. mRNA levels of each gene were quantified using a real time, hydrolysis probe-dependent RT-PCR assay ('Taqman'). Results: Expression of GHRH, GHRH-R and GHS-R 1a was absent in all specimens of normal and malignant breast tissue. Ghrelin mRNA was expressed in all samples of normal tissue and cancers, but there was no significant difference between the two. In normal breast tissue there was a significant correlation between ghrelin mRNA levels and those of all genes studied. Weaker correlations were present in the cancers.

c-myc Cox-2 VEGF189 PCNA

Normal ghrelin 0.40* 0.34* 0.41* 0.66**

Malignantghrelin0.56* 0.33* 0.37* 0.15

*p<0.05; **p<0.0005; ***p<0.000005

Conclusion: The universal expression of ghrelin and its association with that of genes implicated in breast tumourigenesis suggests a role for ghrelin in both the maintenance of normal breast tissue and tumourigenesis. The absence of the GHS-R 1a strongly implies that the effects of ghrelin are mediated via a novel receptor. Whether these effects are independent of the GH/IGF-I axis remain to be determined.