Role of PP2Calpha in cell growth, in radio- and chemosensitivity, and in tumorigenicity.
BACKGROUND
PP2Calpha is the representative member of the type 2C family of protein phosphatases, and it has recently been implicated in the regulation of p53-, TGFbeta-, cyclin-dependent kinase- and apoptosis-signaling. To investigate the role of PP2Calpha in cell growth and in radio- and chemosensitivity, wild type and PP2Calpha siRNA-expressing MCF7 cells were subjected to several different viability and cell cycle analyses, both under basal conditions and upon treatment with radio- and chemotherapy. By comparing the growth of tumors established from both types of cells, we also evaluated the involvement of PP2Calpha in tumorigenesis.


RESULTS
It was found that knockdown of PP2Calpha did not affect the proliferation, the clonogenic survival and the membrane integrity of MCF7 cells. In addition, it did not alter their radio- and chemosensitivity. For PP2Calpha siRNA-expressing MCF7 cells, the number of cells in the G0/G1 phase of the cell cycle was reduced, the induction of the G1 block was attenuated, the number of cells in G2/M was increased, and the induction of the G2 block was enhanced. The tumorigenic potential of PP2Calpha siRNA-expressing MCF7 cells was found to be higher than that of wild type MCF7 cells, and the in vivo proliferation of these cells was found to be increased.


CONCLUSIONS
Based on these findings, we conclude that PP2Calpha is not involved in controlling cell growth and radio- and chemosensitivity in vitro. It does, however, play a role in the regulation of the cell cycle, in the induction of cell cycle checkpoints and in tumorigenesis. The latter notion implies that PP2Calpha may possess tumor-suppressing properties, and it thereby sets the stage for more elaborate analyses on its involvement in the development and progression of cancer.
Lammers
Twan
T
Department of Innovative Cancer Diagnosis and Therapy, Clinical Cooperation Unit Radiotherapeutic Oncology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. t.lammers@dkfz.de
Peschke
Peter
P
Ehemann
Volker
V
Debus
Jürgen
J
Slobodin
Boris
B
Lavi
Sara
S
Huber
Peter
P
D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D003037:Cobalt Radioisotopes; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000235:genetics*; D000071636:Protein Phosphatase 2C; D012334:RNA, Neoplasm / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
D003037:Cobalt Radioisotopes; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D004317:Doxorubicin; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C