MESSENGER-RNA EXPRESSION OF LIGANDS OF THE EPIDERMAL-GROWTH-FACTOR-RECEPTOR IN THE UTERUS

Six different ligands of the epidermal-growth-factor receptor (EGFR) h ave been identified in the past. In some cervical squamous-cell carcin omas, an increased amount of proteins binding to the EGFR has been rep orted. In order to identify the mRNA of EGFR ligands (EGFRL), which mi ght be overexpressed in cervical and endometrial cancers, we performed semi-quantitative reverse-transcription/polymerase chain reactions (R T-PCR) for all 6 EGFRL in RNA extracts of normal and malignant tissue samples of the human uterus. PCR products from RNA extracts of 83 pati ents were quantitated relative to the housekeeping gene and internal s tandard pyruvate dehydrogenase by analyzing the PCR kinetics of produc t synthesis. to extracts of normal cervix, the level of mRNA expressio n of the EGFRL was significantly higher than in endometrium. No signif icant difference was detected between normal cervix and cervical carci nomas. However, both in cervical and in endometrial cancers, mRNA expr ession was non-parametrically distributed and in some cervical cancers overexpression of transforming growth factor alpha (TGF-alpha), amphi regulin or EGF was observed. In endometrial cancers, mRNA levels of al l EGFRL were higher than in normal endometrium. This increase was sign ificant (p < 0.005) for TGF-alpha and amphiregulin. Thus, TGF-alpha mR NA is overexpressed in approximately 10% of cervical cancers and in th e majority of endometrial cancers. Since TGF-alpha anti-sense therapy might represent a future strategy in such cancers, we also determined the absolute level of TGF-alpha mRNA expression by quantitative PCR us ing a cloned standard. (C) 1997 Wiley-Liss, Inc.