hMLH1 and hMSH2 expression and BAX frameshift mutations in ovarian cancer cell lines and tumors

被引:17
作者
Colella, G
Vikhanskaya, F
Codegoni, AM
Bonazzi, C
D'Incalci, M
Broggini, M
机构
[1] Mario Negri Inst Pharmacol Res, Dept Oncol, Mol Pharmacol Unit, I-20157 Milan, Italy
[2] Ist Nazl Ric Canc, Dept Expt Oncol, I-16132 Genova, Italy
[3] Univ Milan, Osped San Gerardo, Monza, Italy
关键词
D O I
10.1093/carcin/19.4.691
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The expression of mismatch repair proteins hMSH2 and hMLH1 was investigated in human ovarian cancer cell lines and in biopsies of ovarian carcinomas obtained from 20 patients undergoing surgical operation. By Western blotting analysis hMSH2 protein was detected in all the tumor samples analyzed and in eight out of nine human ovarian cancer cell lines, while hMLH1 was undetectable in four out of 20 ovarian tumors and in five out of nine human ovarian cancer cell lines analyzed. The possible presence of frameshift mutations in the BAX gene, which contains a sequence of eight contiguous guanines in its third exon, was tested in all the samples. All the cell lines presented the normal alleles for the BAX gene while only in one of the tumor samples a heterozygous frameshift mutation was found. The frameshift mutation was associated to a low, almost undetectable, level of BAX protein which was instead present at much higher levels in all the other samples investigated. The results indicate that frameshift mutations in the BAX gene, possibly arising as a consequence of microsatellite instability (detectable in these tumors), is detectable in human ovarian cancer although quantitatively it does not appear to be a major determinant of the low apoptotic response to chemotherapy observed in ovarian cancer cells.
引用
收藏
页码:691 / 694
页数:4
相关论文
共 33 条
[11]   CLINICAL IMPLICATIONS OF THE P53 TUMOR-SUPPRESSOR GENE [J].
HARRIS, CC ;
HOLLSTEIN, M .
NEW ENGLAND JOURNAL OF MEDICINE, 1993, 329 (18) :1318-1327
[12]   P53 MUTATIONS IN HUMAN CANCERS [J].
HOLLSTEIN, M ;
SIDRANSKY, D ;
VOGELSTEIN, B ;
HARRIS, CC .
SCIENCE, 1991, 253 (5015) :49-53
[13]   Microsatellite instability and DNA mismatch repair in human cancer [J].
Karran, P .
SEMINARS IN CANCER BIOLOGY, 1996, 7 (01) :15-24
[14]   DNA-DAMAGE TOLERANCE, MISMATCH REPAIR AND GENOME INSTABILITY [J].
KARRAN, P ;
BIGNAMI, M .
BIOESSAYS, 1994, 16 (11) :833-839
[15]   MICROSATELLITE INSTABILITY IN OVARIAN NEOPLASMS [J].
KING, BL ;
CARCANGIU, ML ;
CARTER, D ;
KIECHLE, M ;
PFISTERER, J ;
KACINSKI, BM .
BRITISH JOURNAL OF CANCER, 1995, 72 (02) :376-382
[16]   Biochemistry and genetics of eukaryotic mismatch repair [J].
Kolodner, R .
GENES & DEVELOPMENT, 1996, 10 (12) :1433-1442
[17]   Absence of deletions but frequent loss of expression of p16(INK4) in human ovarian tumours [J].
Marchini, S ;
Codegoni, AM ;
Bonazzi, C ;
Chiari, S ;
Broggini, M .
BRITISH JOURNAL OF CANCER, 1997, 76 (02) :146-149
[18]   INACTIVATION OF THE TYPE-II TGF-BETA RECEPTOR IN COLON-CANCER CELLS WITH MICROSATELLITE INSTABILITY [J].
MARKOWITZ, S ;
WANG, J ;
MYEROFF, L ;
PARSONS, R ;
SUN, LZ ;
LUTTERBAUGH, J ;
FAN, RS ;
ZBOROWSKA, E ;
KINZLER, KW ;
VOGELSTEIN, B ;
BRATTAIN, M ;
WILLSON, JKV .
SCIENCE, 1995, 268 (5215) :1336-1338
[19]  
MAZARS R, 1991, ONCOGENE, V6, P1685
[20]   A STRONG CANDIDATE FOR THE BREAST AND OVARIAN-CANCER SUSCEPTIBILITY GENE BRCA1 [J].
MIKI, Y ;
SWENSEN, J ;
SHATTUCKEIDENS, D ;
FUTREAL, PA ;
HARSHMAN, K ;
TAVTIGIAN, S ;
LIU, QY ;
COCHRAN, C ;
BENNETT, LM ;
DING, W ;
BELL, R ;
ROSENTHAL, J ;
HUSSEY, C ;
TRAN, T ;
MCCLURE, M ;
FRYE, C ;
HATTIER, T ;
PHELPS, R ;
HAUGENSTRANO, A ;
KATCHER, H ;
YAKUMO, K ;
GHOLAMI, Z ;
SHAFFER, D ;
STONE, S ;
BAYER, S ;
WRAY, C ;
BOGDEN, R ;
DAYANANTH, P ;
WARD, J ;
TONIN, P ;
NAROD, S ;
BRISTOW, PK ;
NORRIS, FH ;
HELVERING, L ;
MORRISON, P ;
ROSTECK, P ;
LAI, M ;
BARRETT, JC ;
LEWIS, C ;
NEUHAUSEN, S ;
CANNONALBRIGHT, L ;
GOLDGAR, D ;
WISEMAN, R ;
KAMB, A ;
SKOLNICK, MH .
SCIENCE, 1994, 266 (5182) :66-71