Expression of cell-cycle mediators in ovarian cancer cells after transfection with p16INK4a, p21WAF1/Cip-1, and p53

被引:15
作者
Ramirez, PT [1 ]
Gershenson, DM [1 ]
Tortolero-Luna, G [1 ]
Ramondetta, LM [1 ]
Fightmaster, D [1 ]
Wharton, JT [1 ]
Wolf, JK [1 ]
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA
关键词
ovarian cancer; cell-cycle mediators; p16(INK4a); p21(WAF1/Cip-1); p53;
D O I
10.1006/gyno.2001.6438
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective. The purpose of this study was to determine whether transfection of ovarian cancer cell lines with recombinant adenoviral vectors containing wild-type p16(INK4a), p21(WAF1/Cip-1), and p53 caused growth inhibition and induction of apoptosis. We also measured the expression of the cell-cycle mediators Bax, Bcl-2, pRb, and mdm-2. Methods. We introduced the wild-type p16(INK4a,) p21(WAF1/Cip-1), and p53 genes into the ovarian cancer cell lines SK-OV-3 (p16(INK4A) and p53 null) and OVCA-420 (p16(INK4a) and p53 wild-type) by adenoviral transfection. Cell growth inhibition was measured over a 10-day period. Induction of apoptosis was tested for both cell lines 48 h after cell transfection. Expression of cell-cycle mediators was evaluated by Western blot analysis and densitometry. Results. Growth inhibition was documented after transfection with p16(INKa), p21(WAF1/Cip), and p53 in both SK-OV-3 cells and OVCA-420 cells. Apoptosis was greatest in SKOV-3 cells after transfection with p53. A significant expression of Bax was only seen in the SKOV-3 cells transfected with p53. The bcl-2 protein was poorly expressed in both cell lines. Expression of pRb was suppressed in OVCA-420 cells transfected with p16(INKa) and p21(WAF1/Cip-1). Infection with Adp16(INKa) and Adp53 led to an increase in the level of mdm-2 in the SK-OV-3 cell line only. Conclusions. In the ovarian cancer cell lines studied, cell growth was inhibited after transfection with p16(INKa), p21(WAF1/Cip-1) and p53. Cell cycle arrest was highest with p53 transfection. The expression of pro-apoptosis proteins was primarily a function of p53 expression. (C) 2001 Academic Press.
引用
收藏
页码:543 / 548
页数:6
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