Comparative expression of tristetraprolin (TTP) family member transcripts in normal human tissues and cancer cell...

The tristetraprolin (TTP) family of tandem zinc finger proteins comprises three members in man and most other mammals, with a fourth expressed in rodents. In mice, gene disruption of TTP itself leads to a systemic inflammatory syndrome that is mediated in large part by over-expression of tumor necrosis factor alpha (TNF). This increased expression is secondary to stabilization of the TNF mRNA in the TTP KO mice, a finding that led to the characterization of TTP as an mRNA binding protein that can promote the removal of the poly(A) tail from selected mRNAs and facilitate their nucleolytic destruction. The other human family members behave similarly to TTP in over-expression studies of transfected cells, but gene disruption experiments have implicated them in different physiological processes. In the present study, we developed a real-time PCR assay for all three human family members that allowed for comparative measurements of all three family members in the same tissues and cells. We used this assay to quantitate expression levels of all three transcripts in a variety of normal human tissues, as well as in the ;;NCI 60", a well characterized panel of human tumor cell lines. Although studies in fibroblasts and macrophages derived from knockout mice have failed to demonstrate compensatory expression of the family members in terms of transcript levels, it remains possible that the different family members can function as ;;TTP equivalents" in certain physiological or pathological circumstances.