PRLR Specific Neutra™ Antibody Products

Prolactin Receptor (PRLR) is the receptor of prolactin (PRL). Its activation involves ligand-induced dimerization, initiating prolactin-dependent signaling pathways. PRLR plays a role in modulating the endocrine and autocrine effects of prolactin in both normal tissue and cancer contexts. Furthermore, PRLR serves as a survival factor for spermatozoa by preventing sperm capacitation through the inhibition of the activation of AKT signaling pathways and SRC kinase activation. Conditions linked with PRLR include hyperprolactinemia and multiple fibroadenomas of the breast. Its biological functions intersect with pathways such as PI3K-Akt signaling and prolactin signaling.

Its Gene ID: 5618, UniProtKB ID: P16471, and OMIM ID: 176761.

PRLR Related Pathway

PRL interacts with PRLR, which lacks intrinsic kinase activity and is part of the class I cytokine receptor superfamily. Canonical PRL-PRLR signaling triggers downstream pathways, including JAK-STAT, MAPK, and AKT. PRLR signaling is crucial for various biological processes, notably mammary gland development and lactation. However, due to PRLR's widespread tissue expression, its aberrant activation has been implicated in the progression of breast, ovarian, and pancreatic cancers. In breast cancer, PRL-induced JAK-STAT signaling contributes to endocrine therapy resistance alongside elevated HER2 levels, by activating oncogenic factors such as FOS.

Fig.1 PRL/PRLR signaling pathways.^{1, 2}

Applications of PRLR Antibodies

• PRLR MAb as an Effective Therapeutic for PRL-Dependent Cancers

Multiple lines of evidence indicate that the hormone PRL can potentially enhance the development of breast and prostate tumors by interacting with its receptor, PRLR. Both in vivo and in vitro, a humanized monoclonal antibody (mAb) that neutralizes the extracellular domain of PRLR has demonstrated effective inhibition of PRL-induced signaling in breast cancer cells. This antibody blocks the proliferation induced by PRL in various cell line models, including those exhibiting autocrine or paracrine PRL activity. A single dose of the PRLR mAb results in the regression of tumor xenografts dependent on PRL and substantially extends the progression-free survival time. Furthermore, administration of the PRLR mAb significantly suppresses PRLR signaling and attenuates tumor growth in a rat mammary cancer model induced by carcinogens and positive for estrogen receptor expression, demonstrating efficacy as a standalone treatment. The observed biological characteristics of the PRLR mAb indicate its potential as an innovative and efficacious therapy for treating cancers dependent on PRL signaling pathways.

• Antagonist PRLR mAb as a Potential Therapeutic Antagonist

To design a novel PRLR antagonist, a hybridoma technique has been employed to develop a series of mAbs. After extensive screening, a mAb is selected for its specific antagonism of PRLR, as determined by ELISA and western blot analyses. Epitope mapping reveals a common binding site between the anti-PRLR mAb and PRL. Furthermore, treatment with the anti-PRLR mAb inhibits PRL-induced phosphorylation of STAT3/5, AKT, and ERK in a dose-dependent manner in both CHO cells expressing PRLR and Nb2 cells, confirming its antagonistic activity. This anti-PRLR mAb holds promise for the treatment of PRL-dependent diseases.

Creative Biolabs provides a diverse array of over 25 engineered antibodies against PRLR, developed using advanced recombinant techniques. Additionally, bespoke customization services are available for designing neutralizing antibodies specifically targeting PRLR, tailored to precise individual requirements.

REFERENCES

1. Standing, David, Prasad Dandawate, and Shrikant Anant. "Prolactin receptor signaling: A novel target for cancer treatment-Exploring anti-PRLR signaling strategies." Frontiers in Endocrinology 13 (2023): 1112987.
2. Distributed Under open access license CC BY 4.0, without modification.