Human androgen‐induced growth factor in prostate and breast cancer cells: its molecular cloning and growth properties

Abstract

Androgen-induced growth factor (AIGF) has hormone-regulated properties in the mouse Shionogi carcinoma cell line. To investigate whether or not it is involved in growth of human hormone-responsive cancers, we isolated the human AIGF gene from a placental genomic library. Genomic analyses suggested that the AIGF gene was about 6.5 kilobases in length containing five exons. The deduced amino acid sequence of human AIGF was completely identical with that of the mouse. RT-PCR analyses showed that prostate and breast cancer cell lines, LNCaP, PC-3, and MCF-7, slightly expressed the AIGF gene. Recombinant AIGF enhanced the growth of the human prostate cancer LNCaP cells, and it also markedly stimulated the growth of fibroblasts. These in vitro findings suggest that AIGF might be a possible autocrine or paracrine factor in hormone-responsive cancers.

Human fibroblast growth factor-18 stimulates fibroblast cell proliferation and is mapped to chromosome 14p11

“…Therefore, we have designated this growth factor as FGF-18. Among all other FGF family members, FGF-18 is most homologous to FGF-8 (Tanaka et al, 1995) and FGF-17 (Hoshikawa et al, 1998). Human FGF-18 shares 60% identity with human FGF-8 and 58% identity with human FGF-17.…”

Increased expression of fibroblast growth factor 8 in human breast cancer

“…Previous work has shown that FGF8 is expressed by prostate and breast cancer cell lines (Schmitt et al, 1996;Tanaka et al, 1995). An involvement in malignant prostate disease has been demonstrated since FGF8 is detected in prostatic cancers, but not in benign prostatic hypertrophy (Leung et al, 1996).…”

FGF8b oncogene mediates proliferation and invasion of Epstein–Barr virus-associated nasopharyngeal carcinoma cells: implication for viral-mediated FGF8b upregulation

“…Androgen signaling is believed to be an important regulatory mechanism of FGF8b upregulation in prostate cancer (Gnanapragasam et al, 2002), as well as breast cancer (Tanaka et al, 1998), and, more recently, in esophageal cancer (Tanaka et al, 2001;Awan et al, 2007). Of particular interest was the unanticipated clinical association of androgen receptor expression and FGF8b expression in breast cancer (but not with estrogen nor progesterone receptor status) (Tanaka et al, 1995(Tanaka et al, , 1998. Esophageal cancer (which has a male to female ratio of 7:1) (Blot et al, 1993) has recently been shown to be clinically associated with androgen dependence (as indicated by elevated serum testosterone, overexpression of androgen receptor, as well as FGF8b overexpression) (Awan et al, 2007).…”

“…FGF8 is known to be essential for embryogenesis (Crossley and Martin, 1995), in particular, for the development/organogenesis of the craniofacial, pharyngeal, brain, cardiac, kidney, urogenital organs and limbs (Heikinheimo et al, 1994;Crossley et al, 1996;Mattila and Harkonen, 2007). Investigation on the involvement of FGF8b in hormone-related cancers was indeed based on the initial discovery of FGF8 (androgen-induced growth factor) in an androgen-dependent mouse mammary carcinoma cell line (Tanaka et al, 1992) and detection of FGF8 overexpression in human breast and prostate cancers (Tanaka et al, 1995;Leung et al, 1996;Gnanapragasam et al, 2002). Further genomic and functional characterization of the FGF8 family demonstrated that the FGF8b isoform (one of the four human FGF8 isoforms: FGF8a, b, e and f (Gemel et al, 1996)) possesses the greatest mitogenic and, more importantly, the greatest transforming activity than the other isoforms, both in vitro and in vivo (MacArthur et al, 1995a(MacArthur et al, , 1995bBlunt et al, 1997;Song et al, 2000;Olsen et al, 2006).…”