Estrogen-dependent growth of a rat pituitary tumor involves, but does not require, a high level of vascular endothelial growth factor.
Long-term (10-week) treatment of Fischer 344 (F344) rats with the synthetic estrogen diethylstilbestrol (DES) increases the level of vascular endothelial growth factor (VEGF) in the pituitary. This is concurrent with the development of a large tumor of the pituitary of F344 rats. A role for VEGF in estrogen-dependent pituitary tumor growth is also supported by the fact that pituitary VEGF level is not increased by estrogen treatment in rats of the tumor-resistant Brown Norway (BN) strain. However, VEGF is not increased by estrogen treatment in an F(1) hybrid of F344 and BN, even though F(1) hybrid rats do form pituitary tumors in response to estrogen. Quantitative trait locus (QLT) mapping reveals that control of estrogen-dependent VEGF expression is linked to the Edpm5 QTL, which was previously identified as a QTL for estrogen-dependent pituitary tumor growth. In contrast, the QTL Edpm2-1 and Edpm9-2, which have been shown to each have a significant effect on estrogen-dependent pituitary mass of a magnitude similar to Edpm5, do not have any effect on VEGF level. Taken together, our results support the association of VEGF expression with growth of the estrogen-induced rat pituitary tumor, as has been reported by others, but they also indicate that there is significant pathways of growth regulation that are independent of high-level VEGF expression.
Cracchiolo
Danny
D
Department of Biological Sciences, Oakland University, 2200 North Squirrel Road, Rochester, MI 48309-4401, USA.
Swick
Jason W
JW
McKiernan
Lucy
L
Sloan
Erica
E
Raina
Supriya
S
Sloan
Charles
C
Wendell
Douglas L
DL
D000818:Animals; D015153:Blotting, Western; D004273:DNA, Neoplasm / Q000032:analysis; D004276:DNA, Satellite / Q000235:genetics; D004054:Diethylstilbestrol / Q000494:pharmacology*; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D019655:Quantitative Trait, Heritable; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D004273:DNA, Neoplasm; D004276:DNA, Satellite; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004054:Diethylstilbestrol