Mxi1, a Myc antagonist, suppresses proliferation of DU145 human prostate cells.
BACKGROUND
Mxi1, an antagonist of c-Myc, maps to human chromosome 10q24-q25, a region altered in a substantial fraction of prostate tumors. Mice deficient for Mxi1 exhibit significant prostate hyperplasia. We studied the ability of Mxi1 to act as a growth suppressor in prostate tumor cells.


METHODS
We infected DU145 prostate carcinoma cells with an Mxi1-expressing adenovirus (AdMxi1) in vitro, and measured Mxi1 expression, cell proliferation, soft agar colony formation, and cell cycle distribution. To explore mechanisms of Mxi1-induced growth arrest, we performed gene expression analysis.


RESULTS
AdMxi1 infection resulted in reduced cell proliferation, reduced soft agar colony formation, and a higher proportion of cells in the G(2)/M phase of the cell cycle. This G(2)/M growth arrest was associated with elevated levels of cyclin B, and reduced levels of c-MYC and MDM2.


CONCLUSIONS
The ability of AdMxi1 to suppress prostate tumor cell proliferation supports a role for Mxi1 loss in the pathogenesis of a subset of human prostate cancers. Prostate 47:194-204, 2001.
Taj
M M
MM
Division of Pediatric Hematology-Oncology, Department of Pediatrics and Communicable Diseases, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
Tawil
R J
RJ
Engstrom
L D
LD
Zeng
Z
Z
Hwang
C
C
Sanda
M G
MG
Wechsler
D S
DS
D000256:Adenoviridae / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D016195:G2 Phase / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008938:Mitosis / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C079440:MXI1 protein, human