A favorable role of prolactin in human breast cancer reveals novel pathway-based gene signatures indicative of tumor differentiation and favorable patient outcome

Abstract

Summary Prolactin (PRL) hormone is known to play a key role in mammary gland development allowing for successful lactation. The role of this hormone in breast tumorigenesis is still controversial. Here, we evaluated PRL protein and gene expression levels in human breast cancer using tissue microarray of 100 breast cancer cases, as well as different publically available human breast cancer gene profiling databases. Interestingly, our results showed a significant downregulation of PRL expression in breast cancer compared to normal adjacent tissue. Moreover, expression of PRL was associated with more differentiated tumors, early stage, smaller tumor size and absence of distant metastasis. Importantly, our results indicate that higher PRL mRNA levels are significantly associated with prolonged relapse-free survival (RFS) in breast cancer patients (P = 3.7 x 10 -9). Additionally, examining expression of PRL pathway-based gene signature composed of PRL, PRLR, Jak2 and Stat5a showed a significant association with more differentiated tumors (P