Abstract
The levels of mRNA for transforming growth factors (TGF alpha and beta) and the epidermal growth factor receptor (EGFR) were determined in 69 human breast carcinomas and 20 biopsies of non-neoplastic breast tissue by dot blot hybridisation analysis. TGF alpha mRNA was detected in 42% of cancers and 44% of non-neoplastic breast tissue at low levels. TGF beta mRNA was found in all breast cancers and non-neoplastic breast tissues, but the levels of TGF beta mRNA were found to be higher in breast cancers (P = 0.01). EGFR mRNA was detected in 55% of breast cancers and in all non-neoplastic breast tissue tested. The presence of EGFR mRNA was inversely related to oestrogen receptor (ER) status (P = 0.0001). Coexpression of TGF alpha and EGFR was observed in 28% of the carcinomas, and significantly more commonly in ER negative tumours (P = 0.01). No significant relationship was found between histological grade, tumour cellularity or tumour desmoplasia and expression of either the TGFs or of EGFR mRNA. High levels of TGF beta were, however, associated with the absence of lymph node metastases at presentation (P = 0.05). Levels of TGF alpha and beta and EGFR mRNA were analysed in relationship to the relapse-free and overall survival of patients with breast cancer, but none was found to predict significantly the outcome in these patients. Longer clinical follow-up and larger numbers of patients are required to determine whether TGFs will prove a useful marker for prognosis in breast cancer patients.
Highlights
The 50 amino acid peptide, TGF alpha, is known to be derived from a 160 amino acid precursor molecule and is capable of binding to the EGF receptor (EGFR) and initiating cell division, as does EGF (Sporn & Roberts, 1985)
We have recently investigated the occurrence of growth factor transcripts in normal breast tissue, benign breast tumours and breast carcinomas and found that mRNA for TGF alpha and its receptor, epidermal growth factor receptor (EGFR), occurred together more
TGF alpha mRNA was measured in 66 carcinomas by dot blot analysis; 28 (42%) contained detectable transcripts
Summary
The 50 amino acid peptide, TGF alpha, is known to be derived from a 160 amino acid precursor molecule and is capable of binding to the EGF receptor (EGFR) and initiating cell division, as does EGF (Sporn & Roberts, 1985). It has been reported that TGF alpha synthesis is regulated via the oestrogen receptor (ER) (Lippman, 1985). To date there has only been a single report on the occurrence of TGF alpha transcripts in solid tumours (Derynck et al, 1987). This showed that a TGF alpha mRNA of 4.5-4.8 kb was present in many different carcinomas, but only two breast cancers were studied. These workers failed to find TGF alpha transcripts in non-malignant adult tissue
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