Simultaneous suppression of epidermal growth factor receptor and c-erbB-2 reverses aneuploidy and malignant phenotype of a human ovarian carcinoma cell line

被引:28
作者
Pack, SD
Alper, ÖM
Stromberg, K
Augustus, M
Özdemirli, M
Miermont, AM
Klus, G
Rusin, M
Slack, R
Hacker, NF
Ried, T
Szallasi, Z
Alper, Ö
机构
[1] NCI, NIH, Human Carcinogenesis Lab, Bethesda, MD 20892 USA
[2] NIAID, Immunopathol Lab, Bethesda, MD 20892 USA
[3] US FDA, Div Therapeut Prot,NCI,NIH, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Bethesda, MD 20014 USA
[4] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD USA
[5] Georgetown Univ, Sch Med, Inst Mol & Human Genet, Vincent T Lombardi Canc Ctr, Washington, DC USA
[6] Georgetown Univ, Sch Med, Pathol Lab, Vincent T Lombardi Canc Ctr, Washington, DC USA
[7] Georgetown Univ, Sch Med, Dept Oncol, Vincent T Lombardi Canc Ctr, Washington, DC USA
[8] Georgetown Univ, Sch Med, Dept Biostat, Vincent T Lombardi Canc Ctr, Washington, DC USA
[9] Harvard Univ, Sch Med, Childrens Hosp Informat Program, Boston, MA 02115 USA
关键词
D O I
10.1158/0008-5472.CAN-03-1982
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47-68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of cultured human ovarian carcinoma cells (NIH:OVCAR-8). We report here that suppression of both EGFR and c-erbB-2 results in regression of aneuploidy and genomic imbalances in NIH:OVCAR-8 cells, restores a more normal phenotype, and results in a more normal gene expression profile. Combined with cytogenetic analysis, our data demonstrate that the regression of aneuploidy is due to the selective apoptosis of double antisense transfected cells with highly abnormal karyotype.
引用
收藏
页码:789 / 794
页数:6
相关论文
共 21 条
[1]   Amplification of C-MYC as the origin of the homogeneous staining region in ovarian carcinoma detected by micro-FISH [J].
Abeysinghe, HR ;
Cedrone, E ;
Tyan, T ;
Xu, J ;
Wang, N .
CANCER GENETICS AND CYTOGENETICS, 1999, 114 (02) :136-143
[2]  
Alper Ö, 2000, INT J CANCER, V88, P566, DOI 10.1002/1097-0215(20001115)88:4<566::AID-IJC8>3.0.CO
[3]  
2-D
[4]   Gene encoding protein elongation factor EEF1A2 is a putative oncogene in ovarian cancer [J].
Anand, N ;
Murthy, S ;
Amann, G ;
Wernick, M ;
Porter, LA ;
Cukier, IH ;
Collins, C ;
Gray, JW ;
Diebold, J ;
Demetrick, DJ ;
Lee, JM .
NATURE GENETICS, 2002, 31 (03) :301-305
[5]  
Bayani J, 2002, CANCER RES, V62, P3466
[6]   RECEPTORS FOR HORMONES AND GROWTH-FACTORS AND (ONCO)-GENE AMPLIFICATION IN HUMAN OVARIAN-CANCER [J].
BERNS, EMJJ ;
KLIJN, JGM ;
HENZENLOGMANS, SC ;
RODENBURG, CJ ;
VANDERBURG, MEL ;
FOEKENS, JA .
INTERNATIONAL JOURNAL OF CANCER, 1992, 52 (02) :218-224
[7]   Epidermal growth factor receptor and c-erbB-2 oncoproteins in tissue and tumor effusion cells of histopathologically different ovarian neoplasms [J].
Harlozinska, A ;
Bar, JK ;
Sobanska, E ;
Goluda, M .
TUMOR BIOLOGY, 1998, 19 (05) :364-373
[8]   Activation of caspase-8 is critical for sensitivity to cytotoxic anti-Fas anti body-induced apoptosis in human ovarian cancer cells [J].
Hayakawa, A ;
Wu, J ;
Kawamoto, Y ;
Zhou, YW ;
Tanuma, S ;
Nakashima, I ;
Suzuki, H .
APOPTOSIS, 2002, 7 (02) :107-113
[9]   COMPARATIVE GENOMIC HYBRIDIZATION FOR MOLECULAR CYTOGENETIC ANALYSIS OF SOLID TUMORS [J].
KALLIONIEMI, A ;
KALLIONIEMI, OP ;
SUDAR, D ;
RUTOVITZ, D ;
GRAY, JW ;
WALDMAN, F ;
PINKEL, D .
SCIENCE, 1992, 258 (5083) :818-821
[10]   Allelic analysis of serous ovarian carcinoma reveals two putative tumor suppressor loci at 18q22-q23 distal to SMAD4, SMAD2, and DCC [J].
Lassus, H ;
Salovaara, R ;
Aaltonen, LA ;
Butzow, R .
AMERICAN JOURNAL OF PATHOLOGY, 2001, 159 (01) :35-42