Alterations in the activity and expression of serine/threonine protein phosphatases during all trans retinoic acid-induced apoptosis in breast cancer cells.
Retinoids exert different effects on malignant cells with various phenomena. They can induce differentiation and apoptosis in various cancer cells. However, the underlying mechanism of these effects is not clear. There are data related to the role of protein phosphatases during retinoid-induced leukemic cell differentiation. The aim of this study was to evaluate effects of the All trans retinoic acid (ATRA) on protein/serine phosphatases during ATRA induced apoptosis in the breast cancer cells. The MTT assay was used to determine drug-mediated cytotoxicity. A cell death detection ELISA kit was used for detection of the DNA fragments. The activity of serine/threonine protein phosphatases was assayed by the serine/threonine phosphatase system. The expression of serine/threonine protein phosphatases was evaluated by Western blot. During ATRA treatment, a significant decrease in the activity of serine/threonine phosphatases 2A, B and C occurred. The decreased activity of PP2A correlated with the up-regulation of PP2A catalytic and PP2A/B gamma, PP2A/B alpha regulatory subunits. The decrease in activity of the PP2B correlated with down-regulation of PP2B catalytic and up-regulation of PP2B regulatory subunit expression. In addition, there was an up-regulation in PP4C and down regulation in PP2C alpha/beta subunits protein expression. We demonstrated clear alteration in the activity and expression of serine/threonine protein phosphatases in breast cancer cells during ATRA treatment, and we suggest that the ATRA-induced apoptosis of the MCF-7 cells is significantly related to the phosphorylation dynamics.
Sanli
Ulus Ali
UA
Department of Medical Oncology, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey. ulusali@med.ege.edu.tr
Uslu
Ruchan
R
Karabulut
Bulent
B
Sezgin
Canfeza
C
Selvi
Nur
N
Aydin
Hikmet Hakan
HH
Saydam
Guray
G
Goker
Erdem
E
Omay
Serdar Bedii
SB
D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D019703:Calcineurin / Q000096:biosynthesis; D002384:Catalysis; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D004396:Coloring Agents / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation
D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D014212:Tretinoin; D004247:DNA; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; C022616:thiazolyl blue