Identification of the p33(ING1)-regulated genes that include cyclin B1 and proto-oncogene DEK by using cDNA microarray in a mouse mammary epithelial cell line NMuMG

Cancer Res. 2002 Apr 15;62(8):2203-9.

Abstract

The candidate tumor suppressor p33(ING1) plays an important role in inducinggrowth arrest at G(0)-G(1) phase of the cell cycle and/or promoting apoptosis in cancerous cells. p33(ING1) is reported to act as a transcriptional cofactor by associating with tumor suppressor p53, HAT, or histone deacetyltransferase, suggesting that p33(ING1) is involved in chromatin-mediated transcriptional regulation. However, the molecular mechanism of p33(ING1)-mediated transcriptional regulation is poorly understood. Here we analyzed expression profiles in mouse mammary epithelial cells (NMuMG) by using a cDNA microarray consisting of 2304 mouse cDNAs after inducing transformation with antisense inhibitor of growth 1 (ING1) in retrovirus vector. The subsequent confirmation of the altered expression levels of the selected genes by semiquantitative reverse transcription-PCR demonstrated that overexpression of the antisense ING1 stimulated expression of 14 genes, which included cyclin B1, 12-O-tetradecanoylphorbol-13-acetate-inducible sequence 11, proto-oncogene DEK, and osteopontin, whereas we have detected transcriptional repression of 5 genes, including TPT1. In addition, adenovirus-mediated overexpression of ING1 in NMuMG cells resulted in down-regulation of cyclin B1, 12-O-tetradecanoylphorbol-13-acetate-inducible sequence 11, DEK, and osteopontin, whereas the levels of TPT1 expression were increased. The further analysis using p53(-/-) SAOS2 cells showed that the p33(ING1)-induced cyclin B1 down-regulation was p53 dependent. Thus, our cDNA microarray analysis suggested that p33(ING1) targets the multiple genes, including proto-oncogene DEK and cyclin B1, at least some of which are regulated in a p53-dependent manner, in the cells undergoing cell growth or apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins
  • Cell Line
  • Cyclin B / biosynthesis
  • Cyclin B / genetics*
  • Cyclin B1
  • DNA, Antisense / genetics
  • DNA, Antisense / pharmacology
  • DNA-Binding Proteins
  • Drosophila Proteins*
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genes, Tumor Suppressor
  • Growth Inhibitors / genetics
  • Growth Inhibitors / physiology
  • Humans
  • Inhibitor of Growth Protein 1
  • Intracellular Signaling Peptides and Proteins
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / physiology*
  • Mice
  • Nuclear Proteins
  • Oligonucleotide Array Sequence Analysis
  • Proteins / genetics
  • Proteins / physiology*
  • Proto-Oncogene Mas
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptors, Eph Family*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Tumor Protein, Translationally-Controlled 1
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology
  • Tumor Suppressor Proteins

Substances

  • CCNB1 protein, human
  • Ccnb1 protein, mouse
  • Cell Cycle Proteins
  • CycB protein, Drosophila
  • Cyclin B
  • Cyclin B1
  • DNA, Antisense
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Growth Inhibitors
  • ING1 protein, human
  • Ing1 protein, mouse
  • Inhibitor of Growth Protein 1
  • Intracellular Signaling Peptides and Proteins
  • MAS1 protein, human
  • Nuclear Proteins
  • Proteins
  • Proto-Oncogene Mas
  • TPT1 protein, human
  • Tpt1 protein, mouse
  • Tumor Protein, Translationally-Controlled 1
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Dek protein, Drosophila
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Eph Family