Loss of prostaglandin E receptors during progression of rat mammary tumors from hormonal dependence to autonomy.
Prostaglandin E (PGE) receptors and PGE-adenylate cyclase responsiveness were measured in tumor samples from a hormone-dependent subline of the transplantable MTW9 rat mammary tumor and from an autonomous subline derived from the hormone-dependent tumor. Scatchard analysis of the equilibrium binding data suggested that the hormone-dependent, slow-growing (MTW9A) tumors contain two major types of binding sites for PGE2: a high-affinity component (Kd less than 10(-9) M) and a low-affinity component [Kd greater than 10(-8) M]. The hormone-autonomous, fast-growing tumors (MTW9D), however, have lost more than 80% of the PG binding sites and exhibited mainly a predominant PGE lower affinity component (Kd greater than 10(-8) M). Loss of PGE receptors in autonomous tumors was not due to in vivo down-regulation of these receptors by excessive production of PGE, since both the hormone-dependent and autonomous tumors endogenously produce and release approximately the same amounts of PGE. Incubation of tumor tissues in vitro with PGE caused a significant stimulation of adenylate cyclase activity in the MTW9A tumors, whereas adenylate cyclase activity was not stimulated in the MTW9D tumors even in the presence of the nonhydrolyzable analogue of GTP, Gpp[NH]p. The results suggest that loss of PGE receptors and PGE-adenylate cyclase responsiveness occurs during progression of mammary tumors from hormonal dependence to autonomy and that the subsequent loss of cyclic AMP is associated with the uncontrolled growth characteristics of the autonomous tumors.
Abou-Issa
H
H
Minton
J P
JP
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000032:analysis; D015232:Dinoprostone; D005260:Female; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000032:analysis* / Q000473:pathology; D009376:Neoplasms, Hormone-Dependent / Q000032:analysis*; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000032:analysis*; D011982:Receptors, Prostaglandin / Q000032:analysis*; D018078:Receptors, Prostaglandin E; D014316:Tritium
D011458:Prostaglandins E; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D014316:Tritium; D006165:Guanylyl Imidodiphosphate; D000242:Cyclic AMP; D015232:Dinoprostone