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Department of Surgery, Division of General Surgery, and Department of Microbiology and Immunology, Lucille Markey Cancer Center, University of Kentucky Medical Center, Lexington, Kentucky 40536
A pentadecadeoxyribonucleotide (5'-AAAGCCCCCCACCAC), complementary to a splice junction site of mRNA for human proliferation-associated nucleolar protein P120, inhibited expression of the P120 gene and the mitogen-induced proliferation of human lymphocytes. The inhibition of P120 gene expression and proliferation was concentration dependent and reached 90% at 200 µM, as measured by [3H]thymidine uptake and by densitometric scanning of Northern (mRNA) and Western (protein) blots of P120. Inhibition was not observed in cells treated with the correspondent nonsense oligomer. P120 antisense oligomer treatment prevented S-phase entry of mitogen-stimulated lymphocytes, as determined by flow cytometric analysis, but did not block G0-G1 transition assessed by morphological blast transformation and induction of [3H]uridine incorporation. Results of this study suggest that P120 expression may be required for the upregulation of nucleolar function necessary for cell proliferation.
1 This work was supported by grant CA49633 from the USPHS-National Cancer Institute.
2 To whom requests for reprints should be addressed, at Combs Research Facility, Rm. 313, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536-0093.
Received 3/12/92. Accepted 7/23/92.
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