1. Institute of Molecular Biology and Biophysics – Subdivision of Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia 2. Novosibirsk State University, Novosibirsk, Russia; Municipal Clinical Hospital No.1, Novosibirsk, Russia 3. Institute of Molecular Biology and Biophysics – Subdivision of Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia
Breast cancer (BC) is the most common cancer among women. It is known that the prolactin receptor (PRLR) may play a role in breast carcinogenesis, but the available data are often contradictory. To get a more complete picture of the relationship between the receptor and mammary gland carcinogenesis, we examined the association between changes in PRLR expression level and tumor subtype (and its main characteristics). To do this, using real-time PCR, we evaluated the level of PRLR mRNA in BC tissue samples and untransformed adjoining tissue samples (89 pairs). Since the androgen receptor (AR) has begun to be seen as a prognostic marker in breast cancer, we also evaluated the association between mRNA levels of AR and PRLR. We found a significant increase in PRLR expression in luminal subtypes; the highest level of PRLR mRNA was detected in luminal A subtype. In HER2-positive ER-, PR-negative BC, the PRLR mRNA level decreases in tumor tissues compared with untransformed tissues. High PRLR expression is also associated with smaller tumor size in luminal B HER2-negative subtype. In ER-, PR-negative tumors, PRLR expression is associated with AR expression: PRLR mRNA level is increased when AR mRNA level is reduced by more than 8 times in triple-negative tumors; in contrast, in HER2-positive subtype it decreases more significantly when AR expression is reduced by more than 3 times. A tendency towards an increase in PRLR expression with an increase in the AR mRNA level was also discovered in luminal subtypes. The level of PRLR expression depends on the age of patients. In luminal A, PRLR expression is higher in patients under 65 years. In contrast, in luminal B HER2-negative and triple-negative BC, reduced PRLR expression was observed in patients under the age of 40 years and under the age of 50 years, respectively. In this group of patients under the age of 40 years with luminal B HER2-negative BC, ER expression was also reduced (0-4 score according to the IHC assay). Thus, PRLR probably plays a different role in the development and progression of BC: in luminal A and luminal B HER2-positive subtypes PRLR may act as an oncogen, and in luminal B HER2-negative and ER-, PR-negative subtypes can play a tumor suppressor role.
Keywords: breast cancer, prolactin receptor, molecular subtypes
Sutherland A., Forsyth A., Cong Y., Grant L., Juan T.H., Lee J.K., Klimowicz A., Petrillo S.K., Hu J., Chan A., Boutillon F., Goffin V., Egan C., Tang P.A., Cai L., Morris D., Magliocco A., Shemanko C.S. (2015) J. Natl. Cancer Inst., 108(3), djv338. CrossRef Scholar google search