PRLR

Overview

PRLR is a type I cytokine transmembrane receptor expressed on the surface of many cell types, including breast epithelial cells.1

PRLR and its ligand, the peptide hormone prolactin (PRL), are classically recognized for their role in mammary gland development and lactation.1

Binding of PRL to PRLR activates the Jak/Stat5, Ras/Raf/MAPK, PI3K/Akt, and Rac pathways.1

Implications in cancer

Breast Cancer

Epidemiological data and preclinical studies suggest a role for PRLR in pathogenesis of breast cancer.

  • Higher than normal levels of circulating PRL are associated with increased breast cancer risk.2
  • Most breast tumors express PRLR, and increased PRLR expression has been noted in malignant versus normal contiguous human breast tissue.3,4
    • Provides an opportunity for tumor-targeting

PRLR is also frequently expressed at high levels in other cancers5,6

PRLR antagonists have been shown to inhibit proliferation of breast cancer cells in vitro and inhibit tumor growth in rodent models in vivo.7,8

  1. Clevenger CV. Role of prolactin/prolactin receptor signaling in human breast cancer. Breast Dis. 2003;18:75-86.
  2. Tworoger SS, Eliassen AH, Sluss P, et al. A prospective study of plasma prolactin concentrations and risk of premenopausal and postmenopausal breast cancer. J Clin Oncol. 2007;25(12):1482-1488.
  3. Touraine P, Martini JF, Zafrani B, et al. Increased expression of prolactin receptor gene assessed by quantitative polymerase chain reaction in human breast tumors versus normal breast tissues. J Clin Endocrinol Metab. 1998;83(2):667-674.
  4. Faupel-Badger JM, Duggan MA, et al. Prolactin receptor expression and breast cancer: relationships with tumor characteristics among pre- and postmenopausal women in a population-based case-control study from Poland. Horm Cancer. 2014;5(1):42-50.
  5. Glasow A, Haidan A, Gillespie J, et al. Differential expression of prolactin receptor (PRLR) in normal and tumorous adrenal tissues: separation of cellular endocrine compartments by laser capture microdissection (LCM). Endocr Res. 1998;24(3-4):857-862.
  6. Yeh YT, Lee KT, Tsai CJ, et al. Prolactin promotes hepatocellular carcinoma through Janus kinase 2. World J Surg. 2012;36(5):1128-1135.
  7. Chen WY, Ramamoorthy P, Chen N, et al. A human prolactin antagonist, hPRL-G129R, inhibits breast cancer cell proliferation through induction of apoptosis. Clin Cancer Res. 1999;5(11):3583-3593.
  8. Damiano JS, Rendahl KG, Karim C, et al. Neutralization of prolactin receptor function by monoclonal antibody LFA102, a novel potential therapeutic for the treatment of breast cancer. Mol Cancer Ther. 2013;12(3):295-305.
  9. Fuh G, Wells JA. Prolactin receptor antagonists that inhibit the growth of breast cancer cell lines. J Biol Chem. 1995;270(22):13133-13137.

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