Decreased C-MYC and BCL2 Expression Correlates with Methylprednisolone-Mediated Inhibition of Raji Lymphoma Growth

Authors: Morris G.; Denardo S.J.; Denardo G.L.; Leshchinsky T.; Wu B.; Mack P.C.; Winthrop M.D.; Gumerlock P.H.

Source: Biochemical and Molecular Medicine, Volume 60, Number 2, April 1997 , pp. 108-115(8)

Publisher: Academic Press

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 of C-MYC and BCL2 is seen. Abnormalities of the tumor suppressor p53, which exerts growth-suppressing and apoptosis-enhancing functions through the transcriptional regulation of downstream genes including CDKN1, GADD45, and BCL2, are also often found. The goal was to determine the modulation of expression of the oncogenes ( C-MYC and BCL2 ), the p53 pathway described above, and the apoptosis marker TGF -beta 1 in 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 for C-MYC and BCL2 were reduced at 1 day following MP and approached control levels 8 days after MP treatment. Expression levels of p53, CDKN1, and GADD45 were moderately and coordinately decreased at 1 day after cessation of MP treatment and remained repressed a week later. TGF -beta 1 exhibited no change in expression levels. These results suggest that decreased expression of C-MYC and BCL2 may play a role in the molecular events that initiate and are responsible for the growth inhibition of Raji lymphoma xenografts by MP.

Language: English

Document Type: Research article

Affiliations: Department of Internal Medicine, University of California, Davis, School of Medicine, Sacramento, California, 95817

Publication date: 1997-04-01

• In this: publication
• By this: publisher
• In this Subject: Anatomy & Physiology ,  Biology ,  Pharmacology ,  Biochemistry
• By this author: Morris G. ;  Denardo S.J. ;  Denardo G.L. ;  Leshchinsky T. ;  Wu B. ;  Mack P.C. ;  Winthrop M.D. ;  Gumerlock P.H.

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