Telang N T, Inoue S, Bradlow H L, Osborne M P
Strang-Cornell Cancer Research Laboratory, Cornell University Medical College, New York, New York, USA.
Adv Exp Med Biol. 1997;400A:409-18. doi: 10.1007/978-1-4615-5325-0_55.
Deregulated expression of Ras and myc oncogenes confers neoplastic transformation in non-tumorigenic mammary epithelial cells. Down-regulation of perturbed biomarkers prior to tumorigenesis may provide a means of effective chemoprevention. In vitro experiments were designed to i) identify specific molecular, endocrine and cellular biomarkers as quantitative end points for preneoplastic transformation, and ii) utilize these end points to evaluate chemopreventive efficacy of selected naturally-occurring and synthetic tumor inhibitors. Stable Ras and myc transfectants exhibited persistent expression of oncogene specific mRNA transcripts, altered estradiol biotransformation and enhanced anchorage-independent growth in vitro prior to tumorigenesis in vivo. Treatment of the transfectants with omega-3-fatty acid, indole-3-carbinol and tamoxifen individually suppressed the perturbed molecular, endocrine and cellular biomarkers in vitro. Thus, suppressed oncogene expression and altered estrogen metabolism may be important determinants for antiproliferative mechanisms in mammary tumor inhibition, providing useful end points for chemopreventive intervention of preneoplasia.
Ras和myc癌基因的失调表达赋予非致瘤性乳腺上皮细胞肿瘤转化能力。在肿瘤发生前下调受干扰的生物标志物可能提供一种有效的化学预防手段。体外实验旨在：i）鉴定特定的分子、内分泌和细胞生物标志物作为肿瘤前转化的定量终点；ii）利用这些终点评估选定的天然和合成肿瘤抑制剂的化学预防效果。稳定的Ras和myc转染子在体内肿瘤发生前，在体外表现出癌基因特异性mRNA转录本的持续表达、雌二醇生物转化改变以及非锚定依赖性生长增强。用ω-3脂肪酸、吲哚-3-甲醇和他莫昔芬分别处理转染子，可在体外抑制受干扰的分子、内分泌和细胞生物标志物。因此，癌基因表达受抑制和雌激素代谢改变可能是乳腺肿瘤抑制中抗增殖机制的重要决定因素，为肿瘤前病变的化学预防干预提供了有用的终点。
