Expression of transforming growth factor beta 1 TGFβ1), -β2, and -β3 by cultured human prostate cells

Abstract

Transforming growth factor beta s (TGF beta s) are members of a superfamily of polypeptides that control cell cycle progression and a variety of other cellular activities. TGF beta family members, -beta 1, -beta 2, and -beta 3, have been identified in prostate. The levels of expression of these TGF beta isotypes have been reported to vary with the pathologic state of the prostate. While the significance of these observations remains to be elucidated there is little doubt that TGF beta s play an important role in controlling growth of the prostate. The prostatic cells expressing TGF beta s have not been identified. This information would provide insight into the physiologic role of TGF beta s and suggest ways that growth control may be altered in prostate disease. We used stromal (PS) and epithelial (PE) cells, cultured from normal human prostate and benign prostatic hyperplasia (BPH), to study the effect of TGF beta s on cell proliferation and TGF beta transcript and protein expression. The proliferation of PS and PE was inhibited by pM quantities of TGF beta 1, -beta 2, and -beta 3. Both cell types expressed transcripts for all three TGF beta isotypes, but PS primarily secreted TGF beta 1, whereas PE secreted more TGF beta 2 than TGF beta 1. These observations suggest that TGF beta s are antiproliferative agents in vivo, and that the stroma is the source of TGF beta 1 while the epithelium is the major source of TGF beta 2 in prostate. There were no significant differences in the growth response to TGF beta s, the TGF beta-isotype expressed, or the amount of TGF beta secreted by cells cultured from normal prostate or BPH.

Transforming growth factor ? in the human prostate: Its role in stromal-epithelial interactions in non-cancerous cell culture

“…TGFb assayed in the conditioned media of separate cultures is mainly, if not entirely, in the active form, demonstrating``autoactivation'' of latent pro-TGFb. These results are in agreement with previous studies reporting expression and secretion of TGFb isoforms by ®broblasts and epithelial cells of human normal prostate in primary culture [12]. In addition, we demonstrate that PNT2 cells, like normal epithelial cells in primary culture, secrete more TGFb2 than ®broblasts, which seems to be the major source for TGFb1 [12].…”

“…These results are in agreement with previous studies reporting expression and secretion of TGFb isoforms by ®broblasts and epithelial cells of human normal prostate in primary culture [12]. In addition, we demonstrate that PNT2 cells, like normal epithelial cells in primary culture, secrete more TGFb2 than ®broblasts, which seems to be the major source for TGFb1 [12]. TGFb is a potent inhibitor of the cell cycle in normal epithelial cells and has a stimulatory or no effect on ®broblasts [2].…”

“…The three isoforms of TGFb are expressed in the prostate [12,13]. In prostate cancer, TGFb1 expression increases in epithelial cells [14±16], whereas sensitivity to its anti-proliferative effect decreases [17] and these modi®cations are correlated with tumor progression [13,18].…”

The Type III Transforming Growth Factor-β Receptor as a Novel Tumor Suppressor Gene in Prostate Cancer

“…The TGF-h signaling pathway has an important role in regulating normal prostate epithelium, inhibiting proliferation, differentiation, and both androgen deprivation-induced and androgen-independent apoptosis (16)(17)(18). During prostate cancer formation, as in other cancers, prostate cancer cells become resistant to the antiproliferative effects of TGF-h (19).…”

Apoptosis and Tumor Progression in Prostate Cancer

“…In normal prostate, the isoforms of transforming growth factor beta (TGFpi-III) are expressed in both stromal and epithelial cells and functions as growth inhibitors [Story et al, 1993[Story et al, ,1996. Both TGFp receptors (TGFp-RI and TGFp-RII) are abundantly expressed in normal prostate epithelial cells and appeared to be downregulated and exhibit progressive reduction of expression in primary cancer, and IjTnph node metastases [Guo and Kyprianou, 1999].…”