Altered p-JAK1 expression is associated with estrogen receptor status in breast infiltrating ductal carcinoma

The mammalian Janus kinase (JAK) family consists of four members, namely JAK1, JAK2, JAK3 and TYK2, which play a critical role in cytokine/growth factor signaling and is increasingly associated with human cancers. Aberrant activation of these non-receptor tyrosine kinases may contribute to carcinogenesis. Herein, we focused on exploring the potential role of p-JAK1 in breast cancer. The expression profiles of p-JAK1 were analyzed in 68 pairs of cancer and non-cancer breast tissues from the same infiltrating ductal carcinoma case by using immunoblotting technique. The results obtained were further correlated with clinicopathological characteristics. Intriguingly, p-JAK1 expression was decreased in 55.9% of breast cancer tissues as compared to the matched non-cancer tissues. Further immunohistochemistry study showed an intense p-JAK1 staining predominantly in adjacent normal breast tissues but not the matched cancer lesions. Decreased p-JAK1 expression in breast cancer tissues was significantly correlated with positive estrogen receptor (ER) status and increased tumor size (p=0.010 and 0.009). We also found that p-JAK1 expression was high in ERalpha-negative breast cancer cell lines but was low in ERalpha-positive breast cell lines. Transfection of ERalpha-positive MCF-7 cells with an ERalpha-specific siRNA upregulated the expression of p-JAK1. In summary, our results indicated that an altered p-JAK1 expression might be involved in the development of breast infiltrating ductal carcinoma in an ERalpha-related manner.