Concomitant Expression of Prolactin Receptor and TGFβ Receptors in Breast Cancer: Association with Less Aggressive Phenotype and Favorable Patient Outcome

Abstract

The epithelial–mesenchymal transition (EMT) process is known to play an essential role in tumor progression, metastasis and resistance to therapy. This report evaluated the prognostic value of co-expression of the receptor for prolactin (PRLR), a suppressor of EMT, and the receptors for transforming growth factor β (TGFβRI and TGFβRII), an inducer of EMT, in association with different clinicopathological parameters using TMA of 102 breast cancer patients and publicly available data on breast cancer patients. Interestingly, the results revealed that malignant tissues had significantly lower levels of concomitant protein expression of these receptors in comparison to normal/benign breast tissue. In addition, a higher level of concomitant expression was also observed in less aggressive breast cancer phenotypes, including low grade tumors, luminal breast cancer subtype, and less advanced stages of the disease (lymph node negative and early stages). Moreover, the results also showed that the expression of a gene signature composed of PRLR/TGFβRI/TGFβRII correlates more with differentiated grade I tumors, and identified a subset of patients showing better survival outcomes evident in luminal B and HER-2 enriched molecular subtypes. Together, these results indicate that loss of the co-expression of PRLR, TGFβRI and TGFβRII is indicative of aggressiveness and poor patient survival outcomes in breast cancer.

New Imidazo[2,1-b][1,3,4]Thiadiazole Derivatives Inhibit FAK Phosphorylation and Potentiate the Antiproliferative Effects of Gemcitabine Through Modulation of the Human Equilibrative Nucleoside Transporter-1 in Peritoneal Mesothelioma

“…Furthermore, prolactin potently inhibits growth factorinduced proliferation of breast cancer cells (32). Preclinical experiments indicate that blocking prolactin signaling leads to activation of mitogen-activated protein kinase and transforming growth factor-β/Smad signaling pathways (33), and concomitant expression of prolactin and TGF-β receptors is associated with a less aggressive phenotype and favorable patient outcome (34). Potential agonistic as well as antagonistic effects of prolactin signaling demonstrate the need for further biological study.…”

Identification of key genes and long non-coding RNA related to bone metastasis in breast cancer by bioinformatics analysis

“…Furthermore, the HSPB1-encoded protein promotes cancer cell proliferation and metastasis, while protecting cancer cells from apoptosis. In addition, prolactin promotes breast cancer bone metastasis [14][15][16]. Expression of the receptor for prolactin can modulate the microenvironment to induce osteoclast formation.…”

Пролактин, Его Физиологическая Функция И Роль В Канцерогенезе Молочной Железы (Обзор Литературы)

“…Крім того, результати свідчать, що експресія генних сигнатур PRLR/TGFβRI/TGFβRII більше корелює з високим диферціюванням пухлини і може бути визначена як більш сприятливий клінічний варіант серед люмінальних B і Her/2-neu-позитивних підтипах РМЗ. Знижена експресія цих показників є індикатором агресивності й поганого клінічного прогнозу [17].…”