Fgf8 (
fibroblast growth factor 8) was initially cloned from a mouse mammary tumor cell line derived from the
androgen-dependent Shionogi
carcinoma 115. The
androgen-inducible expression of Fgf8 in this
tumor controls its
androgen-dependent phenotype, thus stimulating interest in this gene as a possible factor in human
prostate cancer and other
androgen-sensitive
cancers. However, apart from Shionogi
carcinoma 115, the
androgen inducibility of Fgf8 is controversial. In the present study, having not detected
androgen-inducible expression of Fgf8 in other mouse mammary cell lines or mouse prostate, we examined the Shionogi
carcinoma 115-derived S115 cell line for mouse mammary tumor virus (MMTV) insertions or other nearby DNA rearrangements that might explain the
androgen inducibility of Fgf8 in these cells. Southern blotting did not detect MMTV insertions near Fgf8 but did reveal a specific DNA rearrangement 3.7 kb upstream of Fgf8 in S115 cells and in other cells (SC115) independently derived from Shionogi
carcinoma 115. Spectral karyotyping of S115 cells and sequencing of the cloned rearrangement junctions indicate that Fgf8 is involved in a t(5;19) translocation. The chromosome 5 sequence joined to Fgf8 is immediately adjacent to Smr2 (submaxillary gland
androgen-regulated
protein 2) and includes Muc10 (
mucin 10), two genes that we show are
testosterone inducible in S115 cells, suggesting that the
androgen-dependent expression of Fgf8 in Shionogi
carcinoma 115 and derivative cells results from this translocation. Together, these results suggest that
androgen inducibility is not an inherent property of the Fgf8 gene, which has implications regarding this gene's proposed role in the etiology of
hormone-responsive
cancers.