| J Clin Invest. 1997 December 1; 100(11): 2744–2751. doi: 10.1172/JCI119820. | PMCID: PMC508478 |
Activation of the prolactin receptor but not the growth hormone receptor is important for induction of mammary tumors in transgenic mice. H Wennbo, M Gebre-Medhin, A Gritli-Linde, C Ohlsson, O G Isaksson, and J Törnell Department of Physiology, Research Centre for Endocrinology and Metabolism, Göteborg University Medicinaregatan 1F S-413 90 Göteborg, Sweden. Abstract Transgenic mice overexpressing the human growth hormone gene develop mammary carcinomas. Since human growth hormone gene can activate both the growth hormone receptor (GHR) and the prolactin (PRL) receptor (PRLR), it is not clear which receptor system is responsible for the malignant transformation. To clarify the receptor specificity, we created transgenic mice with two different genes: (a) transgenic mice overexpressing the bovine growth hormone (bGH) gene having high levels of bGH only activating the GHR and also high serum levels of IGF-I; and (b) transgenic mice overexpressing the rat PRL (rPRL) gene that have elevated levels of PRL (one line 150 ng/ml and one line 13 ng/ml) only binding to the PRLR and with normal IGF-I levels. When analyzed histologically, all of the PRL transgenic female mice developed mammary carcinomas at 11-15 mo of age. Only normal mammary tissue was observed among the bGH transgenic animals and the controls. Cell lines established from a tumor produced rPRL and expressed PRLR. In organ culture experiments, an auto/paracrine effect of rPRL was demonstrated. In conclusion, activation of the PRLR is sufficient for induction of mammary carcinomas in mice, while activation of the GHR is not sufficient for mammary tumor formation. Full Text The Full Text of this article is available as a PDF (717K). These references are in PubMed. This may not be the complete list of references from this article. - Ben-Jonathan, N; Mershon, JL; Allen, DL; Steinmetz, RW. Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects. Endocr Rev. 1996 Dec;17(6):639–669. [PubMed]
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