FUNCTIONAL EXPRESSION OF VIP RECEPTORS IN NORMAL, IMMORTALIZED AND TRANSFORMED MAMMARY EPITHELIAL-CELLS

The effect of VIP and its related peptides on cAMP production has been characterized: 1) in long term culture of normal human mammary epithelial cells (HMEC); 2) in immortalized and transformed ST cell lines established from normal HMEC after genomic insertion of the large T oncogene of SV40; 3) in the spontaneously immortalized HC-11 cells, a clone isolated from the mouse mammary epithelial cells COMMA-1D, described to exhibit normal morphogenesis in vivo and functional differentiation in vitro. Basal cAMP levels were increased 1.5- to 8.7- fold in mammary epithelial cells (p < 0.001 - 0.05), with a potency EC50 = 0.02 - 0.6 nM VIP. The pharmacological specificity of the VIP receptors coupled to cAMP generation was established according to the following potency sequence: VIP > PACAP-38 > helodermin > PHM, PHV > helospectin 1 >> hpGRF, secretin in HMEC, VIP > PACAP-38 > helodermin > helospectin 1, PHM, PHV > hpGRF > secretin in S1T3 cells, and VIP, PHI, helodermin > PHV > rhGRF > secretin in HC-11 cells. Our data demonstrate the presence of functional, highly sensitive and specific VIP receptors in normal, immortalized and transformed mammary epithelial cells, suggesting a regulatory role for this neuropeptide on the growth, differentiation and function in normal and neoplastic breast tissue.