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J. Biol. Chem., Vol. 281, Issue 33, 23652-23657, August 18, 2006

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Knockdown of MBP-1 in Human Prostate Cancer Cells Delays Cell Cycle Progression^*

Asish K. Ghosh, Robert Steele, and Ratna B. Ray¹

From the Department of Pathology and Cancer Center, Saint Louis University, St. Louis, Missouri 63104

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.

Received for publication, March 28, 2006 , and in revised form, May 22, 2006.

^* This work was supported by Grant CA52799 from the NCI, National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Pathology, Saint Louis University, 1402 South Grand Blvd., St. Louis, MO 63104. Tel.: 314-577-8331; Fax: 314-771-3816; E-mail: rayrb{at}slu.edu.

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