Activation ofFgf8in S115 Mouse Mammary Tumor Cells Is Associated with Genomic Integration of Mouse Mammary Tumor Virus

Abstract

Fgf8is an embryonally expressed mitogenic fibroblast growth factor which has transforming capacity. It is expressed in S115 mouse mammary tumor 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 ofFgf8which seems to be associated with the androgen-maintained malignant phenotype of the cells. S115 cells also contain and express Mtv proviruses known to insertionally activate oncogenes in other tumor cells. Here we studied the possibility of insertional activation ofFgf8in S115 cells by MMTV proviral integration. We demonstrate by Southern blotting that the genomic DNA from DD/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-6 was localized to the DNA fragment containing theFgf8gene. Furthermore, the expression ofFgf8mRNA in DD/Sio tumors and S115 cells was not found in mammary gland or spleen and liver of DD/Sio mice. In S115 cells,Fgf8mRNA expression was induced in parallel to MMTV mRNA by androgen and glucocorticoids which supports the possibility thatFgf8is controlled by the steroid-regulated MMTV-LTR. In conclusion, our data provide evidence that the insertion of MMTV into the DD/Sio tumor DNA is associated with the transcriptional activation ofFgf8in DD/Sio tumor and consequently in S115 mouse mammary tumor cells.