Xu Y, See W A
Department of Urology, University of Iowa Hospitals and Clinics, Iowa City 52242-1089.
Surg Oncol. 1994 Jun;3(3):175-85. doi: 10.1016/0960-7404(94)90047-7.
The effect of two growth factors ellicited in response to surgical woundings (transforming growth factor alpha [TGF alpha] and beta 1) on the regulation of cellular plasminogen activator activity (PAA) in human transitional carcinoma cell lines, with differing baseline PAA (253J--high; 647V--low), was studied. mRNA transcript levels of PA regulatory proteins in both cell lines were responsive to TGF alpha and TGF beta 1. However, both the magnitude and nature of the response differed markedly between the two lines. TGF alpha increased uPA transcript levels in both cell lines in a dose-dependent fashion. In the case of uPA receptor, exogenous TGF alpha concentrations which increased receptor levels over fivefold in the 253J line had no effect on this transcript in the 647V line. This differential responsiveness was even more pronounced for TGF beta 1. TGF beta 1 appeared to increase uPA transcript in the 253J line in a dose dependent manner while decreasing transcript levels in the 647V line. uPAr mRNA in 253J cells increased over a 19-fold range in response to TGF beta 1 while this same transcript was decreased 14-fold in 647V cells. The most pronounced effect of TGF beta 1 was seen on PAI1 transcript levels in the 253J line. This transcript increased in a concentration dependent fashion from non-detectable levels. These findings demonstrate that growth factors ellicited by surgical wounding may alter the biology of neoplastic cells. Both the growth factor milieu, and intrinsic cellular regulatory mechanism, appear important in determing net PAA in transitional carcinoma cell lines.
研究了手术创伤引发的两种生长因子（转化生长因子α [TGFα] 和β1）对人移行癌细胞系中细胞纤溶酶原激活物活性（PAA）调节的影响，这些细胞系具有不同的基线PAA（253J——高；647V——低）。两种细胞系中PA调节蛋白的mRNA转录水平对TGFα和TGFβ1均有反应。然而，两条细胞系之间反应的程度和性质存在显著差异。TGFα以剂量依赖性方式增加了两种细胞系中uPA的转录水平。就uPA受体而言，在253J细胞系中使受体水平增加五倍以上的外源性TGFα浓度对647V细胞系中的该转录本没有影响。这种差异反应性在TGFβ1的情况下更为明显。TGFβ1似乎以剂量依赖性方式增加253J细胞系中uPA的转录，同时降低647V细胞系中的转录水平。253J细胞中的uPAr mRNA因TGFβ1增加了19倍以上，而在647V细胞中该转录本减少了14倍。TGFβ1对253J细胞系中PAI1转录水平的影响最为显著。该转录本从不可检测水平开始以浓度依赖性方式增加。这些发现表明，手术创伤引发的生长因子可能会改变肿瘤细胞的生物学特性。生长因子环境和内在细胞调节机制在决定移行癌细胞系中的净PAA方面似乎都很重要。
