A direct mechanistic link between growth control and a tumor cell immune function: increased interleukin-8 secretion accounts for elimination of Oct-1 antisense transformants from scid mice.
BACKGROUND
Tumorigenesis involves the aberrant function of proteins that regulate growth control, including Oct-1. Oct-1 is a DNA binding transcription factor that activates genes that encode proteins required for S-phase and cell growth. For example, Oct-1 activates the histone H2B promoter and the promoters for the snRNPs. Oct-1 also represses certain promoters, including promoters of immune function genes, such as the IL-8 and the HLA-DRA genes.


RESULTS
Oct-1 antisense transformants were determined to have reduced growth rates and other characteristics of growth control. Also, Oct-1 antisense transformants endured for a shorter time in scid mice, being attributable to the increased expression of IL-8 by the Oct-1 antisense transformants.


CONCLUSIONS
These results may help resolve the conundrum of why growth control de-regulation alone is not enough for tumorigenicity. The results also support the conclusion that the molecular mechanisms of growth control de-regulation and tumor cell immune functions are directly linked.
Palubin
Kimberly M
KM
Department of Molecular Medicine and College of Medicine, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612, USA.
Goodwin
Bonnie L
BL
Niesen
Melissa I
MI
Le
Elizabeth A
EA
Osborne
Aaron R
AR
Blanck
George
G
D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics / Q000276:immunology; D016373:DNA, Antisense / Q000235:genetics; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D050811:Octamer Transcription Factor-1 / Q000235:genetics*; D014170:Transformation, Genetic; D014183:Transplantation, Heterologous; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
D016373:DNA, Antisense; D016209:Interleukin-8; D050811:Octamer Transcription Factor-1