Immunohistochemical evalulation of activated Ras and Rac1 as potential downstream effectors of aquaporin-5 in breast cancer in vivo

• Published in: Biochemical and biophysical research communications 2017-11, Vol.493 (3), p.1210-1216
• Main Authors: Jensen, Helene H., Login, Frédéric H., Park, Ji-Young, Kwon, Tae-Hwan, Nejsum, Lene N.
• Format: Article
• Language: English
• Subjects: AQP5; Aquaporin 5 - metabolism; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - pathology; Female; Humans; IHC; Immunohistochemistry; Labeling scoring; rac1 GTP-Binding Protein - metabolism; Rac1-GTP,Ras-GTP; ras Proteins - metabolism; Signal Transduction
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.09.125

Aberrant levels of aquaporin-5 (AQP5) expression have been observed in several types of cancer, including breast cancer, where AQP5 overexpression is associated with metastasis and poor prognosis. In cultured cancer cells, AQP5 facilitates cell migration and activates Ras signaling. Both increased cell migration and Ras activation are associated with cancer metastasis, but so far it is unknown if AQP5 also affects these processes in vivo. Therefore, we investigated if high AQP5 expression in breast cancer tissue correlated with increased activation of Ras and of Rac1, which is a GTPase also involved in cell migration. This was accomplished by immunohistochemical analysis of invasive ductal carcinoma of breast tissue sections from human patients, followed by qualitative and quantitative correlation analysis between AQP5 and activated Ras and Rac1. Immunohistochemistry revealed that activation of Ras and Rac1 was positively correlated. There was, however, no correlation between high AQP5 expression and activation of Ras, whereas a nonsignificant, but positive, tendency between the levels of AQP5 and activated Rac1 levels was observed. In summary, this is the first report that correlates AQP5 expression levels to downstream signaling partners in breast cancer tissue sections. The results suggest Rac1 as a potential downstream signaling partner of AQP5 in vivo. [Display omitted] •Subcellular AQP5 localization is altered in human breast cancer.•Correlation analysis of GTPase activation and AQP5 in human breast cancer.•Positive tendency for correlation between Rac-GTP and AQP5 in human breast cancer.•Ras-GTP and Rac1-GTP positively correlated in human breast cancer.