This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gibson, S. L. Articles by Enders, G. H. Search for Related Content PubMed PubMed Citation Articles by Gibson, S. L. Articles by Enders, G. H.

Inhibition of Colon Tumor Progression and Angiogenesis by the Ink4a/Arf Locus¹

Department of Medicine, Gastrointestinal Division, Department of Genetics, and Abramson Cancer Center [S. L. G., C. Y. D., G. H. E.], Department of Medicine, Division of Hematology-Oncology, and Abramson Cancer Center [M. S. G., W. M. F. L.]; Departments of Pathology and Medicine [E. E. F.]; and Department of Biostatistics and Epidemiology [C. B.] University of Pennsylvania, Philadelphia, Pennsylvania 19104; Sungkyunkwan University, Suwon, Republic of Korea [H-W. L.]; and Dana-Farber Cancer Institute, Boston, Massachusetts [R. A. D.]

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.

This article has been cited by other articles:

				E. J. Chapman, P. Harnden, P. Chambers, C. Johnston, and M. A. Knowles Comprehensive Analysis of CDKN2A Status in Microdissected Urothelial Cell Carcinoma Reveals Potential Haploinsufficiency, a High Frequency of Homozygous Co-deletion and Associations with Clinical Phenotype Clin. Cancer Res., August 15, 2005; 11(16): 5740 - 5747. [Abstract] [Full Text] [PDF]

				B. SIMON and N. LUBOMIERSKI Implication of the INK4a/ARF Locus in Gastroenteropancreatic Neuroendocrine Tumorigenesis Ann. N.Y. Acad. Sci., April 1, 2004; 1014(1): 284 - 299. [Abstract] [Full Text] [PDF]