| First Author | Gibson SL | Year | 2003 |
| Journal | Cancer Res | Volume | 63 |
| Issue | 4 | Pages | 742-6 |
| PubMed ID | 12591718 | Mgi Jnum | J:81942 |
| Mgi Id | MGI:2450383 | Citation | Gibson SL, et al. (2003) Inhibition of colon tumor progression and angiogenesis by the ink4a/arf locus. Cancer Res 63(4):742-6 |
| abstractText | 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 influenceof 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 particularly significant in light of the clinical importance of this property in the detection, recurrence, and therapy of colon tumors. |
