Growth stimulatory angiotensin II type-1 receptor is upregulated in breasthyperplasia and in situ carcinoma but not in invasive carcinoma

Two different receptors which bind angiotensin II specifically have been id entified in humans and were designated angiotensin II type-1 receptor (AT(1 )) and angiotensin II type-2 receptor (AT(2)). They only have 34% sequence homology and act through different signalling pathways. AT(1) stimulation h as been implicated in hypertrophy and hyperplasia in various tissues. In or der to study the involvement of AT(1) in tissues from controls (n=10) and p atients with hyperplasia (n=33), ductal carcinoma in situ (DCIS) (n=23) and invasive carcinoma of the breast (n=25), we tested biopsies and breast-der ived cell lines using immunocytochemistry, in situ hybridisation and cell p roliferation techniques. The results show specific overexpression of AT(1) receptor on the cytoplasmic membrane of cells of hyperplastic lesions with and without atypia and on DCIS of the breast. Evidence for growth stimulati on is provided by in vitro experiments showing growth induction by angioten sin II of T47D cells which express the AT(1) but not the AT(2) receptor. Th e expression of AT(1) on the cell membrane disappears in invasive breast ca ncer cells suggesting a regulatory pathway which is no longer needed in inv asive carcinoma. The specific AT(1) expression upregulation might well be a n important step in the pathogenesis of hyperplasia of the breast, which is regarded as a precursor lesion for breast cancer.