Spady T J, Harvell D M, Lemus-Wilson A, Strecker T E, Pennington K L, Vander Woude E A, Birt D F, McComb R D, Shull J D
Eppley Institute for Research in Cancer and Allied Diseases, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, USA.
J Nutr. 1999 Feb;129(2S Suppl):587S-590S. doi: 10.1093/jn/129.2.587S.
We are investigating the mechanisms through which estrogens induce development of prolactin (PRL)-producing pituitary tumors and mammary carcinomas in rats and how these mechanisms are affected by dietary energy consumption. The hypothesis under examination is that dietary energy restriction inhibits tumorigenesis in estrogen-responsive tissues by altering cellular responsiveness to estrogenic hormones. In the Fischer 344 (F344) rat strain, a 40% restriction of energy consumption virtually abolishes development of estrogen-induced pituitary tumors. Inhibition of pituitary tumorigenesis in the F344 strain by energy restriction results from modulation of estrogen regulation of cell survival, not cell proliferation. In contrast, energy restriction has no inhibitory effect on estrogen-induced pituitary tumor development in the ACI rat strain. However, energy restriction markedly inhibits induction of mammary carcinomas in female ACI rats treated with 17beta-estradiol. Data presented herein indicate that dietary energy restriction modulates the responsiveness of specific cell populations to estrogenic hormones and thereby inhibits estrogen-induced tumorigenesis in a manner specific to both rat strain and tissue.
我们正在研究雌激素诱导大鼠产生催乳素（PRL）的垂体肿瘤和乳腺癌发生发展的机制，以及这些机制如何受到饮食能量消耗的影响。正在检验的假设是，饮食能量限制通过改变细胞对雌激素的反应性来抑制雌激素反应性组织中的肿瘤发生。在Fischer 344（F344）大鼠品系中，40%的能量消耗限制实际上消除了雌激素诱导的垂体肿瘤的发生。能量限制对F344品系垂体肿瘤发生的抑制作用是通过调节雌激素对细胞存活的调控，而非细胞增殖。相比之下，能量限制对ACI大鼠品系中雌激素诱导的垂体肿瘤发展没有抑制作用。然而，能量限制显著抑制了用17β-雌二醇处理的雌性ACI大鼠中乳腺癌的诱导。本文提供的数据表明，饮食能量限制调节特定细胞群体对雌激素的反应性，从而以一种对大鼠品系和组织都具有特异性的方式抑制雌激素诱导的肿瘤发生。
