Shionogi Carcinoma 115 (SC115) is an androgen‐sensitive transplantable mouse tumor. To study the mode of progression from androgen‐sensitive to ‐insensitive tumor, cloned SC115 cells were serially cultured without androgen. Shortly after withdrawal of androgen, SC115 cells showed markedly decreased growth, but growth resumed gradually with loss of response to androgen and the cells 60 weeks after androgen removal [A(—)60 cells] grew faster than SC115 cells cultured in the presence of androgen. A(—)60 cells showed malignant phenotype with morphological changes and tumorigenicity in male and female mice. Although mRNA and binding capacity of androgen receptor were maintained, the cells after removal of androgen rapidly lost expression of mouse mammary tumor virus‐related gene and the loss was irreversible in A(—)60 cells. The stimulating effect of basic flbroblast growth factor (bFGF) temporarily decreased, then recovered to the initial level after long‐term androgen removal. This fluctuation of response to bFGF was accompanied with changes in the number of bFGF receptors and amount of bFGF‐like substance(s) secreted. The substance(s) seemed to be an FGF‐like growth factor different from known factors. It was concluded that progression of SC115 cells to androgen‐insensitive ones under an androgen‐deprived condition proceeded with adaptation by means of increases in production of an FGF‐like growth factor and in binding capacity to this factor.
Shionogi carcinoma 115 (SC 115) cells and Chiba subline 2 (CS 2) cells are clones of an androgen-responsive mouse tumor cell line and its autonomous subline, respectively. We have shown previously that CS 2 cells produce a heparin-binding growth factor that stimulates the growth of SC 115 cells as well as the growth of themselves. In this study, a growth factor was purified from serum-free conditioned media of CS 2 cells cultured without testosterone. A heparin-binding fraction showed growth-promoting activity on SC 115 cells and BALB/3T3 cells. The amino acid sequence analysis revealed that the components were identical to histones H2A.1 and H2A.X. Since histone H2A purified from bovine thymus had almost no growth-promoting activity on SC115 cells, histone H2A.X was assumed to be a growth factor. cDNA of histone H2A.X was cloned from a library of CS 2 cells, and its sequence was confirmed. The expressed product of histone H2A.X cDNA in Escherichia coli showed remarkable stimulatory effects on growth of SC 115 cells cultured in the absence of testosterone. These results indicate that histone H2A.X is secreted from CS 2 cells cultured without testosterone and plays a role as a growth factor.
Suramin has been shown to inhibit the binding of various growth factors to their receptors.Shionogi Carcinoma 115 cells (SC 115 cells) and Chiba Subline 2 cells (CS 2 cells) are clones of an androgen-responsive mouse tumor cell and its autonomous subline, respectively. Since the growth of SC 115 and CS 2 cells are assumed to be regulated by their own fibroblast growth factor (FGF)-like growth factors, the present study was undertaken to examine the effect of suramin on these cells.Suramin inhibited the growth of SC 115 and CS 2 cells in a dose dependent manner. The inhibition of suramin was reversible up to 50 pg/ml. Suramin reversibly changed the shape of these cells from fibroblast-like to polygonal and epithelial-like ones, and inhibited 3H-thymidine incorporation into these cells which was evoked by acidic and basic FGFs, and conditioned medium obtained from CS 2 cells. The binding of 125I-basic FGF to SC 115 and CS 2 cells was inhibited by suramin. However, suramin had no effect on growth factor production and the hst-1 gene expression on CS 2 cells. In conclusion, suramin inhibited the autocrine and paracrine growth of SC 115 and CS 2 cells by blocking the binding of autocrine growth factors to their receptors.
Shionogi Carcinoma 115 (SC 115) and Chiba Subline 2 (CS 2) are an androgen‐dependent mouse tumor and an androgen‐independent subline derived from SC 115, respectively. Since new expression of the transforming oncogene hst‐1 might be related with autonomous progression in CS 2, the present study was designed to examine the influence of expression of hst‐1 gene on SC 115. The transfectants of SC 115 with hst‐1 still retained androgen sensitivity of growth, although the cells could grow without androgen. The transfectants, however, developed fibroblast‐like appearance in the absence of androgen, in contrast to SC 115, which showed epithelial‐like appearance after deprivation of androgen. The transfectants acquired an ability to form colonies in soft agar in the absence of androgen. SC 115 could not form tumors in intact mice, but the transfectants formed tumors at a high rate in male mice but not in female ones. From these results, it was concluded that expression of hst‐1 was able to alter the phenotype of the androgen‐dependent tumor with partial loss of androgen‐dependency, and these changes might be advantageous for malignant progression.
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