DecreasedC-MYCandBCL2Expression Correlates with Methylprednisolone-Mediated Inhibition of Raji Lymphoma Growth

Abstract

Methylprednisolone (MP) and related corticosteroids are a fundamental part of regimens used to treat lymphoma and leukemia. In many of these malignancies, oncogenic activation ofC-MYCandBCL2is seen. Abnormalities of the tumor suppressorp53,which exerts growth-suppressing and apoptosis-enhancing functions through the transcriptional regulation of downstream genes includingCDKN1, GADD45,andBCL2,are also often found. The goal was to determine the modulation of expression of the oncogenes (C-MYCandBCL2), thep53pathway described above, and the apoptosis markerTGF-β₁in the human Raji lymphoma following MP treatment. Raji xenografts were grown in nude mice and growth curves characterized by sequential measurement. Mice were treated daily for 8 days with MP. Tumors were harvested untreated, or at 1 or 8 days after cessation of MP treatment, and the RNA was extracted. RT–PCR was used to determine the level of mRNA expression of the genes. Tumor growth was greatly reduced in the MP-treated mice. Gene expression levels forC-MYCandBCL2were reduced at 1 day following MP and approached control levels 8 days after MP treatment. Expression levels ofp53, CDKN1,andGADD45were moderately and coordinately decreased at 1 day after cessation of MP treatment and remained repressed a week later.TGF-β₁exhibited no change in expression levels. These results suggest that decreased expression ofC-MYCandBCL2may play a role in the molecular events that initiate and are responsible for the growth inhibition of Raji lymphoma xenografts by MP.