Inhibition of colon tumor progression and angiogenesis by the Ink4a/Arf locus

Steven L. Gibson, Charlotte Y. Dai, Han Woong Lee, Ronald A. DePinho, Michael S. Gee, William M.F. Lee, Emma E. Furth, Colleen Brensinger, Greg H. Enders

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37 Citations (Scopus)

Abstract

The Ink4a/Arf locus is frequently methylated in colon carcinoma and other common human cancers, suggesting that the locus may play a broad, as yet poorly defined, role inhibiting tumor progression. We examined the influence of the locus in mice with multiple intestinal neoplasia (Min). Colon tumors in 3-month-old Min mice that were null for the Ink4a/Arf locus (-/-) were moderately larger than in Ink4a/Arf-wild-type (+/+) animals (P = 0.032). More strikingly, one-half of the -/- colon tumors were grossly red in color, whereas most of the +/+ tumors were white (P = 0.0025). This color difference remained statistically significant after normalizing for tumor area (P = 0.016). On histological analysis, -/- colon tumors displayed more RBCs near the tumor surface, twice the number of functional vessels, and features of carcinoma in situ not found in +/+ tumors. Biochemical analyses showed that red tumors had higher hemoglobin and vascular endothelial growth factor (VEGF) content than white tumors. Surprisingly, the small intestinal tumor burden was actually lower in -/- animals, and none of these tumors were red, underscoring the importance of tissue context in the function of the locus. These results provide direct evidence that the Ink4a/Arf locus inhibits colon tumor progression. The enhanced vascularity of the -/- tumors is particlarly significant in light of the clinical importance of this property in the detection, recurrence, and therapy of colon tumors.

Original languageEnglish
Pages (from-to)742-746
Number of pages5
JournalCancer Research
Volume63
Issue number4
Publication statusPublished - 2003 Feb 15

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Colon
Neoplasms
Color
Wild Animals
Carcinoma in Situ
Tumor Burden
Vascular Endothelial Growth Factor A
Hemoglobins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Gibson, S. L., Dai, C. Y., Lee, H. W., DePinho, R. A., Gee, M. S., Lee, W. M. F., ... Enders, G. H. (2003). Inhibition of colon tumor progression and angiogenesis by the Ink4a/Arf locus. Cancer Research, 63(4), 742-746.
Gibson, Steven L. ; Dai, Charlotte Y. ; Lee, Han Woong ; DePinho, Ronald A. ; Gee, Michael S. ; Lee, William M.F. ; Furth, Emma E. ; Brensinger, Colleen ; Enders, Greg H. / Inhibition of colon tumor progression and angiogenesis by the Ink4a/Arf locus. In: Cancer Research. 2003 ; Vol. 63, No. 4. pp. 742-746.
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Gibson, SL, Dai, CY, Lee, HW, DePinho, RA, Gee, MS, Lee, WMF, Furth, EE, Brensinger, C & Enders, GH 2003, 'Inhibition of colon tumor progression and angiogenesis by the Ink4a/Arf locus', Cancer Research, vol. 63, no. 4, pp. 742-746.

Inhibition of colon tumor progression and angiogenesis by the Ink4a/Arf locus. / Gibson, Steven L.; Dai, Charlotte Y.; Lee, Han Woong; DePinho, Ronald A.; Gee, Michael S.; Lee, William M.F.; Furth, Emma E.; Brensinger, Colleen; Enders, Greg H.

In: Cancer Research, Vol. 63, No. 4, 15.02.2003, p. 742-746.

Research output: Contribution to journalArticle

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Gibson SL, Dai CY, Lee HW, DePinho RA, Gee MS, Lee WMF et al. Inhibition of colon tumor progression and angiogenesis by the Ink4a/Arf locus. Cancer Research. 2003 Feb 15;63(4):742-746.