We have investigated the individual roles of unmodified prolactin (U-PRL) and a mimic of phosphorylated PRL (S179D PRL) in mammary development. Recombinant versions of the PRLs were delivered to rats throughout pregnancy at a rate of 6 microg/24 h per rat and to non-pregnant females at a rate of 24 microg/24 h per rat. Measurement of progesterone, corticosterone, and estradiol showed no effect of the administered PRLs on the levels of these other mammotropic hormones. Histological and morphometric analysis showed U-PRL to cause mammary growth, whereas S179D PRL inhibited growth. Molecular analysis demonstrated decreased beta-casein expression in the mammary glands of the U-PRL-treated animals at term and increased beta-casein expression in the mammary glands of the S179D PRL-treated animals. Superior beta-casein gene expression in response to S179D PRL versus U-PRL was confirmed in HC11 cells. We conclude that U-PRL is important for growth, whereas S179D PRL promotes at least one measure of differentiated function in the mammary gland.
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http://dx.doi.org/10.1007/s00441-002-0598-8 | DOI Listing |
J Cancer Sci Clin Ther
October 2020
Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 92521, USA.
Calcitriol has been shown to have multiple anti-prostate cancer effects both and in xenograft models, and associations between low levels of calcitriol and more aggressive forms of prostate cancer have been observed clinically. However, the concentrations of calcitriol required to have a substantive anti-cancer effect are toxic. In previous work, we had observed that the selective prolactin receptor modulator, S179D PRL, sensitized prostate cancer cells to physiological concentrations of calcitriol through an ability to increase expression of the vitamin D receptor.
View Article and Find Full Text PDFCancer Lett
June 2016
Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA. Electronic address:
Even though mutations in the tumor suppressor, BRCA1, markedly increase the risk of breast and ovarian cancer, most breast and ovarian cancers express wild type BRCA1. An important question is therefore how the tumor-suppressive function of normal BRCA1 is overcome during development of most cancers. Because prolactin promotes these and other cancers, we investigated the hypothesis that prolactin interferes with the ability of BRCA1 to inhibit the cell cycle.
View Article and Find Full Text PDFCancer Lett
March 2015
Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA. Electronic address:
A comprehensive understanding of prolactin's (PRL's) role in breast cancer is complicated by disparate roles for alternatively-spliced PRL receptors (PRLR) and crosstalk between PRL and estrogen signaling. Among PRLRs, the short form 1b (SF1b) inhibits PRL-stimulated cell proliferation. In addition to ligand-dependent PRLRs, constitutively-active varieties, missing the S2 region of the extracellular domain (ΔS2), naturally occur.
View Article and Find Full Text PDFNeuroscience
January 2014
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autonoma de Mexico, Querétaro 76230, Mexico.
Prolactin (PRL) has many functions in the CNS, including neuroprotection. During lactation, the dorsal hippocampus is protected from excitotoxic kainic acid (KA)-induced cellular damage. We have previously reported that systemic pre-treatment with ovine PRL had similar protective effects in female rats.
View Article and Find Full Text PDFOncol Lett
November 2012
Department of Epidemiology and Health Statistics, School of Public Health and Family Medicine;
A mimic of phosphorylated prolactin (S179D PRL) has been demonstrated to inhibit prostate cancer cell growth in vitro and in vivo; however, the mechanisms involved in this process remain unknown. In this study, we identified that a four-day treatment of S179D PRL (1 μg/ml) in human prostate PC3 cancer cells activated JNK, c-fos and c-jun, and led to apoptosis. We also demonstrated that p21/waf1 was upregulated in cells transfected with the human PRL receptor (S1b) following a four-day incubation with S179D PRL (1 μg/ml).
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