Expression of IGF-I in normal and malignant breast tissue and its association with tumour size
CA Laban1, K McCarthy1, W Ogunkolade2, SA Bustin3, R Carpenter1 & PJ Jenkins2
Background:The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis has been increasingly implicated in the development of breast cancer. Previously we have demonstrated the local expression of IGF-I in normal and malignant breast tissue. However the correlation of this local expression with clinical factors has not fully been investigated.
Aims: (i) To quantify the mRNA levels of IGF-I in normal and malignant breast tissue and (ii) to identify any correlation between level of expression of IGF-I and clinical parameters.
Methods: Local Ethical committee approval was obtained. Total RNA was extracted from 29 samples of paired normal and malignant breast tissue. mRNA levels of IGF-I were quantified using a real time RT-PCR assay ('Taqman'). Full clinical details were available for each patient including tumour type, size, grade, nodal status and estrogen (ER) and progesterone receptor (PR) status.
Results: (i) IGF-I was expressed in 27 of 29 normal samples and 26 of 29 malignant breast tissue samples. IGF-I expression was significantly downregulated in the malignant tissue compared to normal tissue (median log copy number/microgrammes total RNA 4.8E+06 vs 2.0E+07 respectively; P<0.0005). This confirms our previous data. (ii) IGF-I mRNA expression was significantly increased in the larger cancers (>20mm) compared to smaller cancers (<20mm) (1.2E+07 vs 2.9E+06 respectively; P<0.02). There was no association between IGF-I expression and different tumour type, grade, nodal status or ER and PR status.
Conclusion: IGF-I mRNA is expressed locally in normal and malignant breast tissue. The upregulation in larger cancers is in keeping with its mitogenic role and suggests it might play an important role in tumour invasiveness and angiogenesis.