Hsd17b8-KO Mouse

HSD17B8, also known as estradiol 17-beta-dehydrogenase 8, is an enzyme that converts estradiol to estrone through its NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity [1]. It is also involved in acyl thioester metabolism, participating in processes like mitochondrial fatty acid synthesis, peroxisomal β-oxidation of fatty acids, and mitochondrial oxidation of 3R-hydroxyacyl-groups [2,4].

In C. elegans, the loss of the PTEN homolog daf-18 triggers cell division during L1 arrest. Forward genetic screening identified F12E12.11, an ortholog of human HSD17B8, which impacts cell proliferation independently of PTEN's typical phosphatase activity. PTEN physically interacts with HSD17B8, and the reduction in estrone levels and accumulation of estradiol may arrest tumor cells in the G2/M phase of the cell cycle through MAPK/ERK [1]. In breast cancer, HSD17B8 is a protective gene; higher expression means a better prognosis [3].

In conclusion, HSD17B8 plays a significant role in steroid metabolism and cell proliferation regulation. Its interaction with PTEN provides insights into tumor suppression mechanisms. The protective role of HSD17B8 in breast cancer indicates its potential importance in cancer research, highlighting the value of model-based research in understanding its functions and implications in disease.