Panoply™ Human PRLR Knockdown Stable Cell Line

Prolactin (PRL) signaling is upregulated in hormone-responsive cancers. The PRL receptor (PRLR) is a class I cytokine receptor that signals through the Janus kinase (JAK) — signal transducer and activator of transcription and mitogen-activated protein kinase (MAPK) pathways, regulating cell proliferation, migration, stem cell characteristics, and apoptosis. Plasma PRL levels are elevated in patients with pancreatic ductal adenocarcinoma (PDAC). Here, researchers investigated whether PRLR signaling promotes pancreatic tumor growth in mice. PRLR levels are elevated in PDAC compared with non-tumor pancreatic tissue. Co-culturing pancreatic cell lines with PRL activates signaling through JAK2–signal transducer and activator of transcription 3 and extracellular signal–regulated kinase, promoting pancreatic sphere formation and cell migration. These activities were not observed in cells with PRLR knockdown. Pancreatic cancer cells with PRLR knockdown formed significantly smaller tumors in mice. Researchers identified several antipsychotic drugs from the diphenylbutylpiperidine class that inhibit PRL-induced JAK2 signaling. Incubating pancreatic cancer cells with these compounds inhibited their proliferation and the formation of pancreatic spheroids. Injection of one of the compounds, penfluridol, slowed the growth of xenograft tumors in different mouse models, reduced tumor cell proliferation, and induced autophagy.

To demonstrate the importance of PRLR signaling for PDAC growth, researchers knocked down the PRLR gene in MiaPaCa-2 and UNKC-6141 cells (Figure 1A). Western blot analysis of PRL-treated MiaPaCa-2 cells revealed that phosphorylation of STAT3, AKT, and ERK1/2 was not induced in PRLR-knockdown cells (Figure 1B). Compared with controls, PRLR-knockdown MiaPaCa-2 and UNKC-6141 cells exhibited reduced clonogenicity, and sphere size and number were reduced in PRLR-knockdown cells (Figures 1C-E). Furthermore, PRLR knockdown impaired cell migration (Figure 1F). Taken together, these data demonstrate that PRLR signaling is crucial for PDAC growth and migration. Antagonizing PRLR results in reduced ovarian tumor growth in mice.

Figure 1. PRLR knockdown affects PDAC growth. (Dandawate P, et al., 2020)