Constitutive expression of FGF2/bFGF in non‐tumorigenic human prostatic epithelial cells results in the acquisition of a partial neoplastic phenotype

Fibroblast growth factor 2 (FGF2), also known as basic fibroblast growth factor (bFGF), belongs to the FGF family, which consists of at least 9 closely related members. FGF2 is a potent mitogen for fibroblasts derived from normal prostate and, to a lesser extent, for prostatic epithelial cells. Its role in the physiology of the normal prostate seems to be limited to stromal cells, whereas in prostate cancer FGF2 may also have an autocrine/paracrine effect on epithelial cells. In order to better understand the effects of FGF2 on the prostatic epithelium, especially its role in the progression of prostate cancer by establishing an autocrine‐stimulation loop, we transfected FGF2 cDNA into a human prostatic epithelial cell line, PNT1A, immortalized with SV40 large‐T antigen. This cell line is non‐tumorigenic and expresses a high‐affinity FGF2 receptor, FGFR1/flg. We characterized 3 independent FGF2‐transfected clones and found that the establishment of an FGF2 autocrine loop on these cells led to (i) serum‐independent growth, (ii) increased proliferation and (iii) anchorage‐independent growth. Such results argue in favor of the possible action of FGF2 on progression of prostate cancer via an FGF2 autocrine loop on epithelial cells. Int. J. Cancer 72:543–547, 1997. © 1997 Wiley‐Liss, Inc.

[1]  D. Neal,et al.  Peptide growth factors in the prostate as mediators of stromal epithelial interaction. , 1996, British journal of urology.

[2]  M. Brawer,et al.  Serum basic fibroblast growth factor in men with and without prostate carcinoma , 1995, Cancer.

[3]  P. Boyle,et al.  Geographical and temporal patterns of incidence and mortality from prostate cancer. , 1995, Urology.

[4]  P. Viganò,et al.  Basic fibroblast growth factor and ovarian cancer , 1995, The Journal of Steroid Biochemistry and Molecular Biology.

[5]  O. Cussenot,et al.  Functional expression of sv40 in normal human prostatic epithelial and fibroblastic cells - differentiation pattern of nontumorigenic cell-lines. , 1995, International journal of oncology.

[6]  K. Crickard,et al.  Basic fibroblast growth factor and receptor expression in human ovarian cancer. , 1994, Gynecologic oncology.

[7]  D. Birnbaum,et al.  Expression of the FGFR1 gene in human breast‐carcinoma cells , 1994, International journal of cancer.

[8]  O. Cussenot,et al.  Immunocytochemical comparison of cultured normal epithelial prostatic cells with prostatic tissue sections. , 1994, Experimental cell research.

[9]  M. T. Story,et al.  Characteristics of FGF-receptors expressed by stromal and epithelial cells cultured from normal and hyperplastic prostates. , 1994, Growth factors.

[10]  T. Kurokawa,et al.  Molecular cloning of a novel cytokine cDNA encoding the ninth member of the fibroblast growth factor family, which has a unique secretion property , 1993, Molecular and cellular biology.

[11]  P. Maher,et al.  Expression of basic fibroblast growth factor and its receptor in an invasive bladder carcinoma cell line , 1993, Journal of cellular physiology.

[12]  D. Johnson,et al.  Structural and functional diversity in the FGF receptor multigene family. , 1993, Advances in cancer research.

[13]  J. Simard,et al.  Intracrinology: the basis for the rational design of endocrine therapy at all stages of prostate cancer. , 1993, European urology.

[14]  K. Matsumoto,et al.  Cloning and characterization of an androgen-induced growth factor essential for the androgen-dependent growth of mouse mammary carcinoma cells. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[15]  P. Brodt,et al.  Rat prostate adenocarcinoma cells disseminate to bone and adhere preferentially to bone marrow-derived endothelial cells. , 1992, Cancer research.

[16]  R. Coombes,et al.  Expression of basic fibroblast growth factor, FGFR1 and FGFR2 in normal and malignant human breast, and comparison with other normal tissues. , 1992, British Journal of Cancer.

[17]  L. Yeoman,et al.  Identification of basic fibroblast growth factor sensitivity and receptor and ligand expression in human colon tumor cell lines , 1992, Journal of cellular physiology.

[18]  G. Chodak,et al.  Basic fibroblast growth factor in human prostate cancer cells. , 1992, Cancer research.

[19]  D. Moscatelli,et al.  The FGF family of growth factors and oncogenes. , 1992, Advances in cancer research.

[20]  O. Cussenot,et al.  Immortalization of human adult normal prostatic epithelial cells by liposomes containing large T-SV40 gene. , 1991, The Journal of urology.

[21]  T. Stamey,et al.  Cytostatic effects of suramin on prostate cancer cells cultured from primary tumors. , 1991, The Journal of urology.

[22]  B. Kwon,et al.  bFGF as an autocrine growth factor for human melanomas. , 1988, Oncogene research.

[23]  R. Mitchell,et al.  Expression of human basic fibroblast growth factor cDNA in baby hamster kidney-derived cells results in autonomous cell growth , 1988, The Journal of cell biology.

[24]  J. Michaeli,et al.  Expression of basic fibroblast growth factor mRNA in benign prostatic hyperplasia and prostatic carcinoma , 1988, The Prostate.

[25]  R. Ian Freshney,et al.  Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications , 2010 .

[26]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[27]  J. Fiddes,et al.  Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. , 1986, Science.