Salm S N, Koikawa Y, Ogilvie V, Tsujimura A, Coetzee S, Moscatelli D, Moore E, Lepor H, Shapiro E, Sun T T, Wilson E L
Department of Cell Biology, New York University School of Medicine, New York, New York, USA.
J Cell Physiol. 2000 Dec;185(3):416-24. doi: 10.1002/1097-4652(200012)185:3<416::AID-JCP12>3.0.CO;2-Z.
A prostatic smooth muscle cell line (PSMC1) was established from the dorsolateral prostate of p53 null mice. The cell line is nontumorigenic when inoculated subcutaneously, under the renal capsule or intraprostatically in syngeneic mice. These cells express alpha-smooth muscle actin (alpha-SMA), indicating their smooth muscle origin, and TGF-beta significantly enhances expression of alpha-SMA. The cells express both androgen receptor (AR) mRNA and protein, and respond mitogenically to physiological concentrations of androgens. PSMC1 cells produce significant amounts of TGF-beta, which stimulates growth by an autocrine mechanism. Dihydrotestosterone (DHT) increases proliferation of PSMC1 cells by promoting TGF-beta secretion. Considering the significant inhibitory effect of TGF-beta on prostatic epithelial cells and its stimulatory effect on the PSMC1 cells, we postulate that TGF-beta produced by prostatic smooth muscle cells may have a paracrine effect on the prostatic epithelium. We also postulate that TGF-beta may be involved in the etiology of benign prostatic hyperplasia (BPH) by stimulating excessive stromal proliferation. Line PSMC1 is the first reported androgen-responsive murine smooth muscle cell line. It will be useful for in vivo and in vitro experiments to study the mechanisms of androgen action on prostatic stroma and for delineating the interactions that occur between prostatic smooth muscle and epithelium that may lead to prostatic diseases such as BPH.
从p53基因敲除小鼠的背外侧前列腺建立了一种前列腺平滑肌细胞系(PSMC1)。当将该细胞系皮下接种、肾包膜下接种或前列腺内接种于同基因小鼠时,其不具有致瘤性。这些细胞表达α-平滑肌肌动蛋白(α-SMA),表明其平滑肌起源,并且转化生长因子-β(TGF-β)可显著增强α-SMA的表达。这些细胞同时表达雄激素受体(AR)的mRNA和蛋白,并对生理浓度的雄激素有丝裂原反应。PSMC1细胞产生大量的TGF-β,通过自分泌机制刺激生长。双氢睾酮(DHT)通过促进TGF-β分泌增加PSMC1细胞的增殖。考虑到TGF-β对前列腺上皮细胞有显著抑制作用,而对PSMC1细胞有刺激作用,我们推测前列腺平滑肌细胞产生的TGF-β可能对前列腺上皮有旁分泌作用。我们还推测TGF-β可能通过刺激基质过度增殖而参与良性前列腺增生(BPH)的病因学。PSMC1细胞系是首个报道的雄激素反应性小鼠平滑肌细胞系。它将有助于体内和体外实验,以研究雄激素对前列腺基质的作用机制,以及描绘前列腺平滑肌和上皮之间可能导致诸如BPH等前列腺疾病的相互作用。