Fig 1. Potential mechanisms of autocrine Prl-induced prostate tumorigenesis.

Mouse and human prostate epithelia are schematically represented. As determined using Pb-PRL transgenic mice¹⁵, phosphorylated Stat5 (p-Stat5) colocalized with proliferating (Ki-67 positive) luminal cells (represented in blue). As the latter also produce Prl and express the PrlR, this suggests that proliferation of this compartment is mediated by direct autocrine/paracrine effects. The mechanisms underlying proliferation of the basal/stem cell compartment has yet to be elucidated. Since the basal cell marker p63 did not colocalize with p-Stat5, this either suggests that any direct effect of Prl on this compartment could be mediated by signaling pathways other than Stat5, and/or that indirect effects could involve Prl-induced production/secretion of certain growth factor(s) from other cell compartments (stroma, luminal cells). Similar mechanisms may take place in the human prostate, as increased production of local Prl and p-Stat5 have been correlated with Gleason score (see text). In contrast to the mouse, where basal cells are maintained and even amplified in Prl-induced prostate tumors, human prostate tumors lose basal cell markers (p63) in favor of tumor makers (AMACR) never shown in mouse prostate. Effects of Prl on human prostate basal cells have not been documented to our knowledge.