Prostate Hyperplasia in a Transgenic Mouse with Prostate-Specific Expression of Prolactin

Abstract

Prolactin (PRL) is one of several polypeptide factors known to exert trophic effects on the prostate. We have previously reported a dramatic prostate enlargement with concurrent chronic hyperprolactinemia and elevated serum androgen levels in a PRL transgenic mouse (Mt-PRL) with ubiquitous expression of the transgene. To address the role of local PRL action in the prostate, a new transgenic mouse model (Pb-PRL) was generated using the prostate-specific rat probasin (Pb) minimal promoter to drive expression of the rat PRL gene. Pb-PRL transgenic males developed a significant enlargement of both the dorsolateral and ventral prostate lobes evident from 10 wk of age and increasing with age. Expression of the transgene was restricted to the prostate and detected from 4 wk of age. Low levels of transgenic rat PRL were detectable in the serum of adult Pb-PRL animals. Serum androgen levels were normal. The Pb-PRL prostate displayed significant stromal hyperplasia, ductal dilation, and focal areas of epithelial dysplasia. Quantitative analysis of prostatic tissue cellularity demonstrated a marked increase in the stromal to epithelial ratio in all lobes of Mt-PRL and Pb-PRL transgenic prostates compared with controls. Microdissections demonstrated an increased ductal morphogenesis in dorsolateral and ventral prostate lobes of Mt-PRL prostate vs. Pb-PRL and controls. In conclusion, this study indicates the ability of PRL to promote, directly or indirectly, ductal morphogenesis in the developing prostate and further to induce abnormal growth primarily of the stroma in the adult gland in a setting of normal androgen levels.

JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

“…Nevertheless, the summarized data provide a generalized view of the implication of the central cytokine signaling in tumor development of [33] and inhibitory role in metastasis progression [45] ). Moreover, it can help us to decipher new mechanisms of activation of the components of the JAK-STAT pathway like receptor and/ or ligand nuclear localization.…”

“…A constitutively active mutant of JAK2 has been identified in patients with polycythaemia vera [32] . Moreover, increased levels of correspondent ligands can be associated with JAK-STAT induced carcinogenesis: in animal models of prostate and mammary gland hyperplasia with local overexpression of Prl [33,34] ; in humans hyperprolactinemia is considered as a risk factor for breast and, probably, prostate cancer [35,36] ; overexpression of GH in transgenic mice leads to increased frequency of mammary adenocarcinoma [37] . A particular and essential role for neoplasia progression of autocrine production of Prl has been revealed [34,38] .…”

Gene expression profiles of ductal versus acinar adenocarcinoma of the prostate

“…CD24 is a potential oncogene reported to be overexpressed in a large variety of human malignancies. 31 We selected the prolactin receptor for further characterization, as this polypeptide growth factor-receptor axis has been implicated in the development of the normal, 32,33 hyperplastic, 34 and neoplastic 35 prostate. We found the prolactin receptor to be overexpressed in ductal versus acinar adenocarcinoma at both the transcript level and at the protein level, as validated by immunohistochemistry.…”

“…We found the prolactin receptor to be overexpressed in ductal versus acinar adenocarcinoma at both the transcript level and at the protein level, as validated by immunohistochemistry. Whether the prolactin receptor might affect ductal adenocarcinoma growth to a greater degree than acinar adenocarcinoma is not known, but it is of interest that prolactin promotes ductal morphogenesis 34 and an increase in volume of ductal epithelium 32 in rodent prostates. It should be noted that the prolactin receptor, although overexpressed in ductal compared with acinar adenocarcinoma, does not seem to be practical marker in immunohistochemistry for ductal adenocarcinoma, because of the overlap in immunopositivity in ductal and acinar adenocarcinomas.…”

Effect of Prolactin on the Population of Epithelial Cells From Ventral Prostate of Intact and Cyproterone Acetate‐Treated Peripubertal Rats: Stereological and Immunohistochemical Study

“…In addition to the influence of steroid hormones, the action of nonsteroid hormones on the prostate is a potential field of interest, as a relationship between levels of prolactin (PL) and the increase of prostate pathology in men (Bartke, 2004) and rats (Wennbo et al, 1997;Kindblom et al, 2003) has been observed. Moreover, PL stimulates the androgen-independent growth of rat prostate cells in vitro (Ahonen et al, 1999).…”