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 language | English |
|---|---|
| Pages (from-to) | 742-746 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 63 |
| Issue number | 4 |
| Publication status | Published - 2003 Feb 15 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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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 journal › Article
TY - JOUR
T1 - Inhibition of colon tumor progression and angiogenesis by the Ink4a/Arf locus
AU - Gibson, Steven L.
AU - Dai, Charlotte Y.
AU - Lee, Han Woong
AU - DePinho, Ronald A.
AU - Gee, Michael S.
AU - Lee, William M.F.
AU - Furth, Emma E.
AU - Brensinger, Colleen
AU - Enders, Greg H.
PY - 2003/2/15
Y1 - 2003/2/15
N2 - 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.
AB - 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.
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M3 - Article
VL - 63
SP - 742
EP - 746
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 4
ER -