ANDROGEN RECEPTOR GENE MUTATION IN MALE BREAST-CANCER
ANDROGEN RECEPTOR GENE MUTATION IN MALE BREAST-CANCER
复制标题
DOI：
10.1093/hmg/2.11.1799
复制
发表时间：
1993-11-01
影响因子：
3.5
通讯作者：
SULTAN, C
中科院分区：
文献类型：
--
作者：
LOBACCARO, JM;LUMBROSO, S;SULTAN, C
我们筛选了13例男性乳腺癌中存在生殖系突变的外显子2和3编码的雄激素受体的DNA结合域。这两个外显子是从患者白色血细胞中提取的基因组DNA中扩增出来的。在这13例患者中，单链构象多态性和直接测序检测到一个鸟嘌呤-腺嘌呤点突变的核苷酸2185，改变Arg 608到赖氨酸在一个高度保守的区域的第二锌指的雄激素受体。这种突变发生在一个38岁的男子与部分雄激素不敏感综合征和正常的雄激素结合能力培养生殖器皮肤成纤维细胞。据我们所知，只有一个生殖系精氨酸谷氨酰胺雄激素受体基因突变已被报道在男性乳腺癌的位置607。我们描述的雄激素受体突变沿着Arg 608突变为Lys，表明这种遗传异常不是偶然的：乳腺细胞内雄激素作用的减少可能是由于雄激素对这些细胞的保护作用丧失而导致男性乳腺癌的发展。然而，不能排除突变雄激素受体的DNA结合特性的变化激活雌激素调节基因。
We screened thirteen male breast cancers for the presence of germline mutations in exons 2 and 3 encoding the DNA-binding domain of the androgen receptor. These two exons were amplified from genomic DNA extracted from patients' white blood cells. In one of these thirteen patients, single strand conformation polymorphism and direct sequencing detected a guanine-adenine point mutation at nucleotide 2185 that changes Arg608 into Lys in a highly conserved region of the second zinc finger of the androgen receptor. This mutation occurred in a 38 year old man with partial androgen insensitivity syndrome and normal androgen-binding capacity in cultured genital skin fibroblasts. To our knowledge, only one germline Arg to Gln androgen receptor gene mutation has been previously reported at position 607 in male breast cancer. This androgen receptor mutation along with the Arg608 into Lys mutation we describe, suggests that this genetic abnormality is not fortuitous: a decrease in androgen action within the breast cells could account for the development of male breast cancer by the loss of a protective effect of androgens on these cells. Activation of estrogen regulated genes by the change of DNA-binding characteristics of the mutant androgen receptor cannot, however, be ruled out.