Expression profiles of mRNA transcript variants encoding the human inhibitor of growth tumor suppressor gene family in normal and neoplastic tissues.
The INhibitor of Growth (ING) tumor suppressor gene family is important in regulating cell fate and reads the epigenetic code by interacting specifically with methylated histone H3. Several transcript variants are expressed from the five ING genes but nomenclature for these variants are not consistent in the literature, and very little is known regarding transcript variant expression in normal human tissues and during development. Here we propose a standardized nomenclature for human ING gene family transcript variants and present an expression analysis using real-time quantitative PCR. We establish the steady-state levels of eleven human ING mRNA transcript variants across several fetal, adult, and tumor tissues as well as in cancer-derived cell lines. Consistent with their roles as type II tumor suppressors, we find up to 10,000-fold reduction in many transcript variants in a subset of neoplastic cells. We also find considerable variation in expression levels in different tissues, with up to 1 million-fold higher expression of some ING transcripts in adult, compared to fetal counterparts, particularly in the brain cerebral cortex. These results show differential expression of specific subsets of ING1-5 transcript variants in tissues that may influence the degree to which these variants contribute to epigenetic regulation in cancer and development.
Walzak
Alison A
AA
Department of Biochemistry and Microbiology, PO Box 3055, Stn. CSC, University of Victoria, Victoria, British Columbia, Canada V8W 3P6.
Veldhoen
Nik
N
Feng
Xiaolan
X
Riabowol
Karl
K
Helbing
Caren C
CC
D000293:Adolescent; D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000145:classification / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000145:classification / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000145:classification / Q000235:genetics*
C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins