Knockdown of MBP-1 in human prostate cancer cells delays cell cycle progression.
We have previously shown that MBP-1 acts as a general transcriptional repressor, and forced expression of MBP-1 exerts an anti-proliferative effect on a number of human cancer cells. In this report, we have investigated the role of endogenous MBP-1 in cell growth regulation. For this, we generated human prostate cancer cells (PC3) stably transfected with short hairpin RNA targeting MBP-1. We have observed retarded growth and longer doubling time of MBP-1 knockdown PC3 cells as compared with control mock-transfected PC3 cells. Fluorescence-activated cell sorter analysis suggested that PC3 cells expressing MBP-1-specific small interfering RNA accumulated during G2/M phase of the cell cycle. Further analysis suggested that depletion of MBP-1 was associated with reduction of cyclin A and cyclin B1 expression when compared with that of the control cells. A delayed induction of cyclin A and B1 expression was observed in MBP-1-depleted PC3 cells (PC3-4.2) upon serum stimulation, although the level of expression was much lower than that of control PC3 cells. Supplementation of MBP-1 in PC3-4.2 cells restored cyclin A and cyclin B1 expression. Together, these results suggest that knockdown of MBP-1 in prostate cancer cells perturbs cell proliferation by inhibiting cyclin A and cyclin B1 expression.
Ghosh
Asish K
AK
Department of Pathology, Saint Louis University, St. Louis, Missouri 63104, USA.
Steele
Robert
R
Ray
Ratna B
RB
D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048429:Cell Size; D019925:Cyclin A / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019926:Cyclin B / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D056744:Cyclin B1; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D034622:RNA Interference / Q000502:physiology*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000502:physiology; D014162:Transfection
C534699:CCNB1 protein, human; D019925:Cyclin A; D019926:Cyclin B; D056744:Cyclin B1; D006131:Growth Inhibitors; C499048:MBP protein, human; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors