Em. Valve et al., ACTIVATION OF FGF8 IN S115 MOUSE MAMMARY-TUMOR CELLS IS ASSOCIATED WITH GENOMIC INTEGRATION OF MOUSE MAMMARY-TUMOR VIRUS, Biochemical and biophysical research communications (Print), 250(3), 1998, pp. 805-808
Fgf8 is an embryonally expressed mitogenic fibroblast growth factor wh
ich has transforming capacity. It is expressed in S115 mouse mammary t
umor cells (S115 cells) and in parental tumors of DD/Sio mice as well
as in some human breast and prostate cancer cell lines. In S115 cells
androgens induce the expression of Fgf8 which seems to be associated w
ith the androgen-maintained malignant phenotype of the cells. S115 cel
ls also contain and express Mtv proviruses known to insertionally acti
vate oncogenes in other tumor cells. Here we studied the possibility o
f insertional activation of Fgf8 in S115 cells by MMTV proviral integr
ation. We demonstrate by Southern blotting that the genomic DNA from D
D/Sio tumors and S115 cells contains Mtv-sequences (Mtv-6 and Mtv-17)
which are not found in the DNA from spleen or liver of the DD/Sio mice
. In addition, the newly integrated Mtv-g was localized to the DNA fra
gment containing the Fgf8 gene. Furthermore, the expression of Fgf8 mR
NA in DD/Sio tumors and S115 cells was not found in mammary gland or s
pleen and liver of DD/Sio mice. In S115 cells, Fgf8 mRNA expression wa
s induced in parallel to MMTV mRNA by androgen and glucocorticoids whi
ch supports the possibility that Fgf8 is controlled by the steroid-reg
ulated MMTV-LTR. In conclusion, our data provide evidence that the ins
ertion of MMTV into the DD/Sio tumor DNA is associated with the transc
riptional activation of Fgf8 in DD/Sio tumor and consequently in S115
mouse mammary tumor cells. (C) 1998 Academic Press.