The fluorescent probe method has been reported to apply for human lung cancer, especially adenocarcinoma. The fluorescent probe method is a novel technique capable of specifically detecting cancer cells. This study aimed to elucidate the cancer-specific expression mechanism of γ-glutamyl transpeptidase (γ-GTP), a key enzyme serving as the primary molecular target in this detection method.

We choose lung adenocarcinoma cell line, A549, as a positive cell line of the fluorescent probe method, among several human cell lines. This cell line positive for GGT1 were analyzed immunohistochemically to examine the relationship between GGT1 expression and the KRAS and HRAS, and pathways.

KRAS and HRAS were positively expressed in A549, GGT1-positive cell line. The GGT1 inhibition experiment revealed that that GGT1 expression is involved upstream of the RAS signaling pathway. In contrast, GGT1 remained positive in the RAS inhibition experiment, indicating that RAS inhibition had no effect on GGT1 expression. Furthermore, inhibition of GGT1 resulted in a decrease in cell proliferative activity, suggesting that GGT1 may contribute to cancer cell proliferation.

GGT1 was suggested to function upstream of the RAS pathway and to be involved in RAS activation and cell proliferation as a cancer-related protein. Inhibition of GGT1 reduced cell proliferative activity, indicating that GGT1 could serve as a potential target for cancer diagnosis and therapy.