aHIF: a natural antisense transcript overexpressed in human renal cancer and during hypoxia.

Background: Nonpapillary renal carcinoma is the predominant form of human kidney cancer and represents a distinct disease entity, morphologically and molecularly, from papillary renal carcinoma. We have discovered a natural antisense transcript that is complementary to the 3' untranslated region of...

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Publicado en:JNCI: Journal of the National Cancer Institute Vol. 91; no. 2; pp. 143 - 152
Autores principales: Thrash-Bingham, Catherine A., Tartof, Kenneth D., Thrash-Bingham, C A, Tartof, K D
Formato: research Journal Article
Publicado: Oxford University Press / USA 01/20/99
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 01/20/99
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      pub: Oxford University Press / USA
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        10.1093/jnci/91.2.143
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        atl: aHIF: a natural antisense transcript overexpressed in human renal cancer and during hypoxia.
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        au:
          Thrash-Bingham, Catherine A.
          Tartof, Kenneth D.
          Thrash-Bingham, C A
          Tartof, K D
        affil: Fox Chase Cancer Center, Philadelphia, PA, USA
      sug:
        subj:
          Transcription Factors
          Nucleotides Metabolism
          Kidney Neoplasms Metabolism
          DNA-Binding Proteins
          Carcinoma, Renal Cell Metabolism
          Adenocarcinoma Metabolism
          Nuclear Proteins
          Documentation
          Nucleotides
          Reverse Transcriptase Polymerase Chain Reaction
          Proteins
          Genetic Techniques
          Biochemical Phenomena
          RNA Metabolism
          DNA
          Human
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
      ab: Background: Nonpapillary renal carcinoma is the predominant form of human kidney cancer and represents a distinct disease entity, morphologically and molecularly, from papillary renal carcinoma. We have discovered a natural antisense transcript that is complementary to the 3' untranslated region of hypoxia inducible factor alpha (HIF1alpha) messenger RNA (mRNA) and is strikingly overexpressed specifically in nonpapillary kidney cancer. HIF1alpha encodes a protein that is known to have two important functions: 1) to act as a transcription factor for hypoxia inducible genes and 2) to stabilize p53 protein during hypoxia. Because of the importance of HIF1alpha, we have characterized this natural antisense transcript, which we have named "aHIF."Methods: Differential display, reverse transcription-polymerase chain reaction, ribonuclease protection, and DNA-sequencing methods were used in our analysis.Results and Conclusions: We show the following: 1) aHIF is a natural antisense transcript derived from HIF1alpha gene sequences encoding the 3' untranslated region of HIF1alpha mRNA; 2) aHIF is specifically overexpressed in all nonpapillary clear-cell renal carcinomas examined, but not in the papillary renal carcinomas examined; 3) aHIF is overexpressed in an established nonpapillary renal carcinoma cell line under both normoxic (i.e., normal aerobic) and hypoxic conditions; and 4) although aHIF is not further induced by hypoxia in nonpapillary disease, it can be induced in lymphocytes where there is a concomitant decrease in HIF1alpha mRNA. To our knowledge, this is the first case of overexpression of a natural antisense transcript exclusively associated with a specific human malignant disease.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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