Antiestrogen inhibition of prolactin-induced growth of the Nb2 rat lymphoma cell line

• Published in: Cancer research (Chicago, Ill.) Ill.), 1989-11, Vol.49 (22), p.6295-6299
• Main Authors: BISWAS, R, VONDERHAAR, B. K
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Binding, Competitive; Biological and medical sciences; Cell Division - drug effects; Cell Line; Estrogen Antagonists - pharmacology; General aspects; Intracellular Membranes - metabolism; Kinetics; Lymphoma - pathology; Medical sciences; Microsomes - drug effects; Microsomes - metabolism; Pharmacology. Drug treatments; Prolactin - pharmacology; Rats; Receptors, Drug; Receptors, Estrogen - drug effects; Receptors, Estrogen - metabolism; Receptors, Somatotropin - drug effects; Receptors, Somatotropin - metabolism; Tamoxifen - metabolism; Tumor Cells, Cultured - cytology; Tumor Cells, Cultured - drug effects
• ISSN: 0008-5472; 1538-7445

The rat lymphoma cell line Nb2 is highly prolactin responsive in terms of growth. Estrogens are without effect in these cells that lack the estrogen receptor. The growth stimulation by lactogenic hormones is effectively inhibited by antiestrogens, such as tamoxifen and nafoxidine, at concentrations as low as 10(-10) M. The growth inhibition is partially reversed by replacement of the antiestrogens by prolactin. Nb2 cells contain estrogen-noncompetitive specific antiestrogen binding sites on their membranes that bind tamoxifen with an average Kd of 3.1 X 10(-10) M. Addition of antiestrogens to the binding reaction inhibits lactogenic hormone binding to membrane-bound receptors. The order of affinities of various antiestrogens (tamoxifen, nafoxidine, 2-(4-tert-butyl-phenoxy)ethyl diethylamine hydrochloride, and LY117018) for the antiestrogen binding sites parallels the order of their potencies as growth and lactogen binding inhibitors. These data suggest that antiestrogens, possibly acting through the antiestrogen binding sites, may function as antilactogens.