EPIDERMAL GROWTH-FACTOR AND TRANSFORMING-GROWTH-FACTOR ALPHA-MESSENGER-RNA EXPRESSION IN HUMAN BREAST-CANCER BIOPSIES - ANALYSIS IN RELATION TO ESTRADIOL, PROGESTERONE AND EGF RECEPTOR CONTENT

Among the peptide growth factors active in breast glandular cell proli feration epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are thought to play a major role in tumour developme nt. They operate through binding to and activation of a common membran e receptor, defined as EGF-R. Their production is modulated by hormone s and local growth factors. After it was shown by previous investigati on in this laboratory that EGF-R could be detected in 90% of the tumou rs, but was masked by endogenous ligand in 36% of them, the question w as raised as to the level of the ligand's expression in tumour tissue biopsies. Therefore, we investigated the expression of EGF and TGF alp ha mRNA in 146 breast cancer biopsies by slot blot analysis using spec ific P-32-labelled probes. The data were correlated with sex steroids and EGF receptor content. Our results showed that EGF and TGF alpha co existed in all tumour samples, and that their level. of mRNA expressio n was similar in half of the tumours. Northern blot and polymerase cha in reaction (PCR) analysis validated these findings. A significant dir ect correlation was found between the level of TGF alpha/EGF mRNA expr ession and the ER/progesterone receptor (PGR) content. TGF alpha and E GF mRNA levels were significantly higher in ER+ (P = 0.0015 and P = 0. 0001, respectively) and in PGR+ tumours (P < 0.005 and P = 0.0001) tha n in their negative counterparts. Moreover, TGF alpha mRNA expression negatively correlated with the number of EGF-R binding sites measured by the standard method (P = 0.02), and it was significantly related to the number of sites occupied by endogenous ligand. In conclusion, it was shown that TGF alpha and EGF mRNA were coexpressed in all the tumo ur biopsies tested and that their level was higher in the hormone rece ptor positive than in negative samples. The correlation between the pr esence of ER/PGR sites, high level of TGF alpha/EGF mRNA and EGF-R occ upancy by endogenous ligand is in favour of ER mediated control of TGF alpha and EGF production. (C) 1997 Elsevier Science Ltd.