Human GHR Stable Cell Line - BaF3

Cancer resistance is observed in both humans and mice when functional growth hormone (GH) receptors are absent. With a focus on lung cancer, the researchers examined the function of the GHRP495T GH receptor variation in the promotion of cancer. They used human lung cell lines and mouse pro-B-cell lines that express themselves consistently to show that GHRP495T extends the duration of the GH signal like autocrine GH action. They discovered that the threonine change at Pro 495 impairs SOCS2-mediated receptor degradation, resulting in elevated surface receptor expression. Mutational study showed that SOCS2 binding was interfered with, changing the adjacent Thr494 and Tyr487 that are essential for SOCS2 contact. This replacement caused structural comparison using nuclear magnetic resonance spectroscopy to reveal changes in the SOCS2 binding site. Crucially, after GH stimulation, lung cells harbouring GHRP495T showed elevated production of tumorigenic genes, indicating a role in the development of cancer.

Figure 1. Using Ba/F3 cells, the researchers examined the effects of GHRP495T and WT GHR expression on cell proliferation. They matched surface receptor levels by using fluorescence-activated cell sorting. Human growth hormone caused GHRP495T to proliferate more, and higher total GHR levels were linked to less breakdown. GHRP495T cells exhibited a large increase in phosphorylated STAT5, a crucial effector of GH-induced proliferation, in contrast to WT GHR cells. (Chhabra Y, et al., 2018)