Peehl D, Wong S, Rhim J
NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702.
Int J Oncol. 1995 Jun;6(6):1177-84. doi: 10.3892/ijo.6.6.1177.
Six lines of human papillomavirus (HPV)-transformed prostatic epithelial cells, clonally-derived from transfection of three different parental cell strains, were analyzed for their ability to respond to stimulatory and inhibitory factors known to regulate prostatic cell growth. The cell lines were tested in a serum-free medium that was developed specifically for analysis of low-density growth of prostatic cells in order to mitigate any effects of autocrine factors. This medium has been used previously to characterize the growth regulatory pathways of primary cultures of prostatic epithelial cells derived from normal, benign prostatic hyperplasia (BPH), or adenocarcinoma tissues, as well as an SV40-transformed cell line (pRNS-1-1) that was derived from the same parental cell strain as four of the HPV-transformed lines used in the present study. The responses of the HPV-transformed cell lines to three essential mitogens in the medium - epidermal growth factor (EGF), bovine pituitary extract (BPE) and insulin-like growth factor (IGF) - were similar to those of primary cultures and pRNS-1-1, except that two of the HPV-transformed cell lines were IGF-independent for growth. The presence or absence of cholera toxin (CT), which acts synergistically with peptide growth factors, only mildly affected the proliferation of HPV-transformed cells, which is also true for primary cultures and pRNS-1-1. However, while hydrocortisone (HC) also has only minimal effect on the growth of primary cultures and pRNS-1-1, four of the HPV-transformed lines were very dependent on HC for growth. With regard to growth-inhibitory factors, all of the cell lines (HPV- or SV40- transformed) were insensitive to tumor necrosis factor-alpha (TNFalpha), which is a common feature of transformed cells. However, the cell lines remained sensitive to the growth-inhibitory properties of retinoic acid (RA) and transforming growth factor-beta (TGF(beta)). The HPV-transformed cell lines were also inhibited by 1,25(OH)(2) vitamin D-3 [1,25(OH)(2)D-3], although pRNS-1-1 cells were not. Perhaps the most unexpected finding in our study was the apparent loss of responsiveness of all of the transformed lines to fibroblast growth factor (FGF). Alterations in FGF pathways have been described for prostatic cancer cell lines and changes in expression of FGF or receptors may be involved in prostatic carcinogenesis. Our study demonstrates that the availability of primary cultures, SV40- and HPV- transformed cell lines and a well-defined culture system will provide an opportunity to characterize the processes involved in malignant transformation of prostatic cells.
对六株人乳头瘤病毒（HPV）转化的前列腺上皮细胞系进行了分析，这些细胞系是通过转染三种不同的亲代细胞株克隆衍生而来的，研究它们对已知调节前列腺细胞生长的刺激因子和抑制因子的反应能力。这些细胞系在一种无血清培养基中进行测试，该培养基是专门为分析前列腺细胞的低密度生长而开发的，以减轻自分泌因子的任何影响。这种培养基先前已用于表征源自正常、良性前列腺增生（BPH）或腺癌组织的前列腺上皮细胞原代培养物以及一种SV40转化细胞系（pRNS-1-1）的生长调节途径，该SV40转化细胞系与本研究中使用的四株HPV转化细胞系源自同一亲代细胞株。HPV转化细胞系对培养基中的三种必需促有丝分裂原——表皮生长因子（EGF）、牛垂体提取物（BPE）和胰岛素样生长因子（IGF）——的反应与原代培养物和pRNS-1-1相似，只是其中两株HPV转化细胞系的生长不依赖IGF。与肽生长因子协同作用的霍乱毒素（CT）的存在与否，仅对HPV转化细胞的增殖有轻微影响，原代培养物和pRNS-1-1也是如此。然而，虽然氢化可的松（HC）对原代培养物和pRNS-1-1的生长也只有最小影响，但四株HPV转化细胞系的生长非常依赖HC。关于生长抑制因子，所有细胞系（HPV或SV40转化的）对肿瘤坏死因子-α（TNFα）均不敏感，这是转化细胞的一个共同特征。然而，这些细胞系对维甲酸（RA）和转化生长因子-β（TGF-β）的生长抑制特性仍然敏感。HPV转化细胞系也受到1,25(OH)₂维生素D-3 [1,25(OH)₂D-3]的抑制，尽管pRNS-1-1细胞不受影响。也许我们研究中最出乎意料的发现是所有转化细胞系对成纤维细胞生长因子（FGF）的反应明显丧失。前列腺癌细胞系中已描述了FGF途径的改变，FGF或其受体表达 的变化可能参与前列腺癌的发生。我们的研究表明，原代培养物、SV40和HPV转化细胞系以及一个定义明确的培养系统的可用性，将为表征前列腺细胞恶性转化所涉及的过程提供机会。
