Ephrin-A1 promotes the malignant progression of intestinal tumors in Apc(min/+) mice.
The ephrin-A1 and EphA receptors are frequently highly expressed in different human cancers, suggesting that they may promote tumor development and progression. We generated transgenic mice carrying Fabpl(4xat-132) ephrin-A1, which express ephrin-A1 in the intestinal epithelial cells. Those mice were then mated with Apc(min/+) mice to produce the compound mice, which overexpress ephrin-A1 in the intestinal tumors of Apc(min/+) mice. We compared the number, size and histopathological features of the intestinal tumors in the Fabpl(4xat-132) ephrin-A1/Apc(min/+) compound mice with those of the Apc(min/+) mice. The compound mice showed an increased number of intestinal tumors, significantly in the large intestine, and developed more invasive tumors. Among the 20 mice of each type examined, 5 Apc(min/+) mice developed 5 invasive tumors, 1 invasive tumor in each mouse, in the proximal or middle portions of the small intestine. On the other hand, 14 out of 20 compound mice developed 29 invasive tumors and 16 of them were in the distal small intestine and the large intestine, where transgenic ephrin-A1 was highly expressed. These results suggested that the increased expression of ephrin-A1 accelerated the malignant progression of the intestinal adenoma to invasive tumors.
Shi
L
L
Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Itoh
F
F
Itoh
S
S
Takahashi
S
S
Yamamoto
M
M
Kato
M
M
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D018450:Disease Progression; D036382:Ephrin-A1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D017491:Genes, APC; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D009378:Neoplasms, Multiple Primary / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D047368:Tumor Burden / Q000235:genetics
D036382:Ephrin-A1; C493320:Fabp1 protein, mouse; D050556:Fatty Acid-Binding Proteins; D011993:Recombinant Fusion Proteins