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

Abstract

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. Materials, Methods and 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. Conclusion: 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.