15-Deoxy- Δ12,14-prostaglandin J2 activates PI3K-Akt signaling in human breast cancer cells through covalent modification of the tumor suppressor PTEN at cysteine 136

15-Deoxy- Δ12,14-prostaglandin J2 (15d-PGJ2), one of the terminal products of cyclooxygenase-2-catalized arachidonic acid metabolism, has been shown to stimulate breast cancer cell proliferation and migration through Akt activation, but the underlying mechanisms remain poorly understood. In the present study , we investigated the effects of 15d-PGJ2 on the activity of PTEN, the inhibitor of the phosphoinositide 3-kinase (PI3K)-Akt axis, in human breast cancer (MCF-7) cells. Since the α,β-unsaturated carbonyl moiety in the cyclopentenone ring of 15d-PGJ2 is electrophilic, we hypothesized that 15d-PGJ2- induced Akt phosphorylation might result from the covalent modification and subsequent inactivation of PTEN that has several critical cysteine residues.

Source: Cancer Letters - March 14, 2018 Category: Cancer & Oncology Authors: Jinyoung Suh, Do-Hee Kim, Eun-Hee Kim, Sin-Aye Park, Jong-Min Park, Jeong-Hoon Jang, Su-Jung Kim, Hye-Kyung Na, Nam-Doo Kim, Nam-Jung Kim, Young Ger Suh, Young-Joon Surh Tags: Original Articles Source Type: research