DECREASED EXPRESSION OF BRCA1 ACCELERATES GROWTH AND IS OFTEN PRESENT DURING SPORADIC BREAST-CANCER PROGRESSION

被引：531
作者：
THOMPSON, ME
JENSEN, RA
OBERMILLER, PS
PAGE, DL
HOLT, JT
机构：
[1] VANDERBILT UNIV, SCH MED, DEPT CELL BIOL, NASHVILLE, TN 37232 USA
[2] VANDERBILT UNIV, SCH MED, DEPT PATHOL, NASHVILLE, TN 37232 USA
[3] VANDERBILT UNIV, SCH MED, DEPT PREVENT MED, NASHVILLE, TN 37232 USA
来源：
NATURE GENETICS | 1995年 / 9卷 / 04期
关键词：
D O I：
10.1038/ng0495-444
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
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.
引用
收藏
页码：444 / 450
页数：7
相关论文
共 26 条
[1]   INTRADUCTAL CARCINOMA - LONG-TERM FOLLOW-UP AFTER TREATMENT BY BIOPSY ALONE [J].
BETSILL, WL ;
ROSEN, PP ;
LIEBERMAN, PH ;
ROBBINS, GF .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1978, 239 (18) :1863-1867
[2]   MUTATIONS IN THE BRCA1 GENE IN FAMILIES WITH EARLY-ONSET BREAST AND OVARIAN-CANCER [J].
CASTILLA, LH ;
COUCH, FJ ;
ERDOS, MR ;
HOSKINS, KF ;
CALZONE, K ;
GARBER, JE ;
BOYD, J ;
LUBIN, MB ;
DESHANO, ML ;
BRODY, LC ;
COLLINS, FS ;
WEBER, BL .
NATURE GENETICS, 1994, 8 (04) :387-391
[3]  
CROPP CS, 1994, CANCER RES, V54, P2548
[4]   CONFIRMATION OF BRCA1 LAY ANALYSIS OF GERMLINE MUTATIONS LINKED TO BREAST AND OVARIAN-CANCER IN 10 FAMILIES [J].
FRIEDMAN, LS ;
OSTERMEYER, EA ;
SZABO, CI ;
DOWD, P ;
LYNCH, ED ;
ROWELL, SE ;
KING, MC .
NATURE GENETICS, 1994, 8 (04) :399-404
[5]   LINKAGE OF EARLY-ONSET FAMILIAL BREAST-CANCER TO CHROMOSOME-17Q21 [J].
HALL, JM ;
LEE, MK ;
NEWMAN, B ;
MORROW, JE ;
ANDERSON, LA ;
HUEY, B ;
KING, MC .
SCIENCE, 1990, 250 (4988) :1684-1689
[6]   AN OLIGOMER COMPLEMENTARY TO C-MYC MESSENGER-RNA INHIBITS PROLIFERATION OF HL-60 PROMYELOCYTIC CELLS AND INDUCES DIFFERENTIATION [J].
HOLT, JT ;
REDNER, RL ;
NIENHUIS, AW .
MOLECULAR AND CELLULAR BIOLOGY, 1988, 8 (02) :963-973
[7]  
HOLT JT, 1993, CANCER SURV, V18, P115
[8]  
JACOBS IJ, 1993, CANCER RES, V53, P1218
[9]   IDENTIFICATION OF GENES EXPRESSED IN PREMALIGNANT BREAST DISEASE BY MICROSCOPY-DIRECTED CLONING [J].
JENSEN, RA ;
PAGE, DL ;
HOLT, JT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (20) :9257-9261
[10]  
Marcus J N, 1994, J Natl Cancer Inst Monogr, P23
123