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Transcriptional response to hypoxia in human tumors.

Publication ,  Journal Article
Lal, A; Peters, H; St Croix, B; Haroon, ZA; Dewhirst, MW; Strausberg, RL; Kaanders, JH; van der Kogel, AJ; Riggins, GJ
Published in: J Natl Cancer Inst
September 5, 2001

BACKGROUND: The presence of hypoxic regions within solid tumors is associated with a more malignant tumor phenotype and worse prognosis. To obtain a blood supply and protect against cellular damage and death, oxygen-deprived cells in tumors alter gene expression, resulting in resistance to therapy. To investigate the mechanisms by which cancer cells adapt to hypoxia, we looked for novel hypoxia-induced genes. METHODS: The transcriptional response to hypoxia in human glioblastoma cells was quantified with the use of serial analysis of gene expression. The time course of gene expression in response to hypoxia in a panel of various human tumor cell lines was measured by real-time polymerase chain reaction. Hypoxic regions of human carcinomas were chemically marked with pimonidazole. Immunohistochemistry and in situ hybridization were used to examine gene expression in the tumor's hypoxic regions. RESULTS: From the 24 504 unique transcripts expressed, 10 new hypoxia-regulated genes were detected-all induced, to a greater extent than vascular endothelial growth factor, a hypoxia-induced mitogen that promotes blood vessel growth. These genes also responded to hypoxia in breast and colon cancer cells and were activated by hypoxia-inducible factor 1, a key regulator of hypoxic responses. In tumors, gene expression was limited to hypoxic regions. Induced genes included hexabrachion (an extracellular matrix glycoprotein), stanniocalcin 1 (a calcium homeostasis protein), and an angiopoietin-related gene. CONCLUSIONS: We have identified the genes that are transcriptionally activated within hypoxic malignant cells, a crucial first step in understanding the complex interactions driving hypoxia response. Within our catalogue of hypoxia-responsive genes are novel candidates for hypoxia-driven angiogenesis.

Duke Scholars

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Published In

J Natl Cancer Inst

DOI

ISSN

0027-8874

Publication Date

September 5, 2001

Volume

93

Issue

17

Start / End Page

1337 / 1343

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tumor Cells, Cultured
  • Transcription, Genetic
  • Time Factors
  • Tenascin
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • In Situ Hybridization
  • Immunohistochemistry
 

Citation

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Lal, A., Peters, H., St Croix, B., Haroon, Z. A., Dewhirst, M. W., Strausberg, R. L., … Riggins, G. J. (2001). Transcriptional response to hypoxia in human tumors. J Natl Cancer Inst, 93(17), 1337–1343. https://doi.org/10.1093/jnci/93.17.1337
Lal, A., H. Peters, B. St Croix, Z. A. Haroon, M. W. Dewhirst, R. L. Strausberg, J. H. Kaanders, A. J. van der Kogel, and G. J. Riggins. “Transcriptional response to hypoxia in human tumors.J Natl Cancer Inst 93, no. 17 (September 5, 2001): 1337–43. https://doi.org/10.1093/jnci/93.17.1337.
Lal A, Peters H, St Croix B, Haroon ZA, Dewhirst MW, Strausberg RL, et al. Transcriptional response to hypoxia in human tumors. J Natl Cancer Inst. 2001 Sep 5;93(17):1337–43.
Lal, A., et al. “Transcriptional response to hypoxia in human tumors.J Natl Cancer Inst, vol. 93, no. 17, Sept. 2001, pp. 1337–43. Pubmed, doi:10.1093/jnci/93.17.1337.
Lal A, Peters H, St Croix B, Haroon ZA, Dewhirst MW, Strausberg RL, Kaanders JH, van der Kogel AJ, Riggins GJ. Transcriptional response to hypoxia in human tumors. J Natl Cancer Inst. 2001 Sep 5;93(17):1337–1343.
Journal cover image

Published In

J Natl Cancer Inst

DOI

ISSN

0027-8874

Publication Date

September 5, 2001

Volume

93

Issue

17

Start / End Page

1337 / 1343

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tumor Cells, Cultured
  • Transcription, Genetic
  • Time Factors
  • Tenascin
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • In Situ Hybridization
  • Immunohistochemistry