Enhancement by prolactin of carcinogen induced mammary cancerigenesis in the male rat

Abstract

Summary.-Mammary tumours were induced in 3 groups of male Long-Evans rats by a series of 6 fortnightly gastric intubations of 7, 12-dimethylbenzanthracene. Two weeks before the initial carcinogen treatment one group of rats was grafted with 3 pituitary homografts underneath the kidney capsule of each recipient (hyperprolactinaemia). A second group, 2 weeks before the initial carcinogen treatment and for the duration of the study (35 weeks), were injected 4x weekly with 2-Br-oaergocryptine (CB-154) (hypoprolactinaemia). A third group of rats served as controls. A significant increase in the incidence of mammary tumours and a reduced latency period of tumour appearance in the hyperprolactinaemia group, when compared with the controls, were observed in this study. Mammary tumour incidence and latency period of tumour appearance in the hypoprolactinaemia group, however, did not differ significantly from controls. Thus, an increased secretion of pituitary prolactin in rats appears to be an important enhancing endocrinic condition in carcinogenesis of the male mammary gland.

Description of the prevalence, histologic characteristics, concomitant abnormalities, and outcomes of mammary gland tumors in companion rats (Rattus norvegicus): 100 cases (1990–2015)

“…Cisplatin is a platinum-based chemotherapeutic agent that has been used to decrease experimentally induced tumor development in the mammary glands of rats in models of human breast cancer. 10,43 In the present study, only 1 rat received intralesional cisplatin, and we cannot draw any conclusions regarding its effectiveness.…”

“…Mammary gland fibroadenomas are associated with prolactinemia in some strains of laboratory rats. [8][9][10][11] Prolactin secretion increases subsequent to a decrease in the secretion of dopamine from the pituitary gland in geriatric rats 12 and persistent low concentrations of progesterone, constant estrus, or cessation of ovulation in female rats. 7,13,14 In some laboratory rat strains, including the Sprague-Dawley, 12 Fisher, 15 and Wistar 16,17 strains, pituitary gland adenomas develop in > 80% of rats > 24 months old.…”

Cancer risk in hyperprolactinemia patients: a population-based cohort study

“…Experimental studies have reported that PRL induces proliferation of breast cancer cells in vitro and enhances growth of mammary carcinoma in rodents and may act as an autocrine or paracrine factor within mammary tissue (5,6). Furthermore, several case reports of breast carcinomas in women and men with prolactinomas have been reported (7)(8)(9) raising the issue of whether high PRL levels are associated with an increased risk of breast cancer.…”

Loss of mammary epithelial prolactin receptor delays tumor formation by reducing cell proliferation in low-grade preinvasive lesions

“…Overexpression of rat Prl using the lipocalin promoter to drive expression predominantly in mammary epithelium produces (ER) positive tumors at a higher rate than other mouse mammary cancer models (Rose-Hellekant et al, 2003). Prl as a modulator of preinitiated cancer has been examined in chemical carcinogenesis (Welsch et al, 1975) and transgenic oncogene models. Prl and Prlr mRNA were detected in nitrosomethylurea (NMU) carcinogeninduced tumors and a rat Prl antiserum inhibited NMU-induced tumor cell proliferation by up to 70%, compared to normal rabbit serum and GH antiserum (Mershon et al, 1995).…”