Aphidicolin inhibits cell proliferation via the p53-GADD45β pathway in AtT-20 cells

Endocrine Journal

Yuko Asari²  Aya Sugiyama²  Kanako Niioka²  Makoto Daimon²  Kazunori Kageyama²  Yutaka Oki¹  Shingo Murasawa² 

[1] Family Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan;Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan

关键词: ACTH;    POMC;    Pituitary;    Cushing’s disease;    Stress;   

DOI  :  10.1507/endocrj.EJ15-0084

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(22)Cited-By(1)Cushing’s disease is primarily caused by pituitary corticotroph adenomas, which autonomically secrete adrenocorticotropic hormone (ACTH).ACTH production may be associated with tumor cell proliferation; however, the effects of cell cycle progression on ACTH production and cell proliferation are little known in corticotroph tumor cells.A DNA polymerase inhibitor, aphidicolin, arrests cells at the entrance to the S phase and blocks the cell cycle; aphidicolin also induces apoptosis in tumor cells.In the present study, we determined ACTH production and cell proliferation of AtT-20 corticotroph tumor cells following treatment with aphidicolin.Aphidicolin decreased proopiomelanocortin mRNA levels in AtT-20 cells and the levels of ACTH in the culture medium of these cells.Aphidicolin also decreased cell proliferation and induced apoptosis in AtT-20 cells.Fluorescence-activated cell sorting analyses revealed that this agent increased the percentage of G0/G1 phase cells, and decreased S phase cells.Aphidicolin decreased the phosphorylation of cyclic adenosine monophosphate response element-binding protein and Akt.Aphidicolin increased the levels of tumor protein 27 (p27) and 53 (p53), while it decreased cyclin E levels.Aphidicolin also increased the mRNA levels of the stress response gene growth arrest and DNA damage-inducible 45β (GADD45β), a putative downstream target of p53.The p53 knockdown increased GADD45β mRNA levels.The GADD45β knockdown inhibited the decreases in cell proliferation. Thus, aphidicolin inhibits cell proliferation via the p53-GADD45β pathway in AtT-20 cells.

【 授权许可】

Unknown