DECREASED EXPRESSION OF BRCA1 ACCELERATES GROWTH AND IS OFTEN PRESENT DURING SPORADIC BREAST-CANCER PROGRESSION
DECREASED EXPRESSION OF BRCA1 ACCELERATES GROWTH AND IS OFTEN PRESENT DURING SPORADIC BREAST-CANCER PROGRESSION
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DOI：
10.1038/ng0495-444
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发表时间：
1995-04-01
期刊：
影响因子：
30.8
通讯作者：
HOLT, JT
中科院分区：
文献类型：
--
作者：
THOMPSON, ME;JENSEN, RA;HOLT, JT
我们的特点表达的家族性乳腺癌和卵巢癌基因，BRCA 1，在非遗传性（散发性）乳腺癌的情况下，并分析了反义抑制BRCA 1对乳腺上皮细胞增殖率的影响。BRCA1 mRNA水平在从原位癌向浸润性癌的转变过程中显著降低。实验用反义寡核苷酸抑制BRCA1表达加速了正常和恶性乳腺细胞的生长，但对非乳腺上皮细胞没有影响。这些研究表明，BRCA1可能通常作为乳腺上皮细胞生长的负调节因子，其功能在乳腺癌中通过直接突变或基因表达的改变而受损。
We have characterized expression of the familial breast and ovarian cancer gene, BRCA1, in cases of non-hereditary (sporadic) breast cancer and analyzed the effect of antisense inhibition of BRCA1 on the proliferative rate of mammary epithelial cells. BRCA1 mRNA levels are markedly decreased during the transition from carcinoma in situ to invasive cancer. Experimental inhibition of BRCA1 expression with antisense oligonucleotides produced accelerated growth of normal and malignant mammary cells, but had no effect on non-mammary epithelial cells. These studies suggest that BRCA1 may normally serve as a negative regulator of mammary epithelial cell growth whose function is compromised in breast cancer either by direct mutation or alterations in gene expression.