Cruz Pamela, Torres Cristian, Ramírez María Eugenia, Epuñán María José, Valladares Luis Emilio, Sierralta Walter Daniel
Laboratorio de Nutrición y Regulación Metabólica, INTA-Universidad de Chile , Santiago 7830489;
Exp Ther Med. 2010 May;1(3):531-536. doi: 10.3892/etm_00000084. Epub 2010 May 1.
The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E(2)) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E(2), and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E(2) in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E(2)-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels.
本研究的目的是确定某些雌激素受体（ER）阳性乳腺肿瘤细胞对抗雌激素或局部雌二醇（E₂）生成抑制剂治疗仍具有抗性的可能机制。为此，我们比较了新型选择性ER调节剂27-羟基胆固醇（27OHC）与E₂对乳腺癌细胞的增殖作用，并评估了ICI 182,780（ICI）对它们的抑制作用。在有无ICI的情况下，分析了27OHC和E₂对细胞周期的影响。在ER阳性乳腺肿瘤细胞中，我们检测到辛伐他汀可阻断27OHC的增殖刺激活性，以及一种甲胎蛋白衍生的环九肽可抑制E₂刺激的增殖。本文报道的作用可能适用于浸润性乳腺癌，其中局部巨噬细胞的活性可能刺激肿瘤生长。我们认为肥胖患者乳腺癌生长增加可能与循环中27OHC水平升高有关。
