Ottaviano Y L, Issa J P, Parl F F, Smith H S, Baylin S B, Davidson N E
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
Cancer Res. 1994 May 15;54(10):2552-5.
Breast cancer is the most common malignancy in women and hormone resistance is a challenging problem in its treatment. Loss of estrogen receptor expression is an important means of hormone resistance, but the mechanisms involved are poorly understood. We now demonstrate a potential role for abnormal DNA methylation in transcriptional inactivation of the estrogen receptor gene. Estrogen receptor-negative human breast cancer cells growing in culture lack estrogen receptor mRNA, have a higher capacity to methylate DNA, and display extensive methylation of the CpG island in the 5' promoter region of the estrogen receptor gene, which would correlate with silencing of expression. These results suggest that abnormal methylation could account for transcriptional inactivation of the estrogen receptor gene and subsequent hormone resistance in some human breast cancers.
乳腺癌是女性中最常见的恶性肿瘤，激素抵抗是其治疗中的一个具有挑战性的问题。雌激素受体表达缺失是激素抵抗的一个重要手段，但其中涉及的机制尚不清楚。我们现在证明了异常DNA甲基化在雌激素受体基因转录失活中的潜在作用。在培养中生长的雌激素受体阴性的人乳腺癌细胞缺乏雌激素受体mRNA，具有更高的DNA甲基化能力，并在雌激素受体基因5'启动子区域的CpG岛显示广泛甲基化，这与表达沉默相关。这些结果表明，异常甲基化可能是某些人类乳腺癌中雌激素受体基因转录失活及随后激素抵抗的原因。
