Suppression of the transformed phenotype of breast cancer by tropomyosin-1

被引:72
作者
Mahadev, K
Raval, G
Bharadwaj, S
Willingham, MC
Lange, EM
Vonderhaar, B
Salomon, D
Prasad, GL
机构
[1] Wake Forest Univ, Bowman Gray Sch Med, Dept Gen Surg, Winston Salem, NC 27157 USA
[2] Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA
[3] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27157 USA
[4] NCI, Ctr Canc Res, Basic Res Lab, Bethesda, MD 20892 USA
关键词
tropomyosin; breast cancer; cytoskeleton; E-cadherin; beta-catenin; tumor suppression;
D O I
10.1006/excr.2002.5583
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Changes in the expression of microfilament-associated proteins, such as tropomyosins (TMs), are commonly found in malignantly transformed cells. Previous work from this laboratory has shown that tropomyosin-1 (TM1) expression is consistently abolished in human breast carcinoma cell lines, suggesting that the loss of TM1 could be a common biochemical event in the transformation of mammary epithelium. To investigate whether changes in TM1 expression are causally linked to mammary carcinogenesis, we have tested the hypothesis that TM1 is a tumor suppressor of breast cancer. MCF-7 cells, which lack TM1, were utilized as a model of human breast cancer and transduced to reexpress TMI. protein. Restoration of TMI expression in MCF-7 cells (MCF-7/T cells) resulted in a slower growth rate, but cells remained sensitive to growth control by estrogen. TMI. expression in MCF-7 cells resulted in the emergence of TM-containing microfilaments. More significantly, MCF-7/T cells failed to grow under anchorage-independent conditions. TM1 reexpression alters the interaction of the E-cadherin-catenin complex with the cytoskeleton, indicating that TM1-induced cytoskeleton could play a significant role in suppression of the malignant phenotype. Taken together with our previous work on transformed murine fibroblasts, the results presented in this communication indicate that in nonmuscle cells TM1. functions as a suppressor of transformation. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:40 / 51
页数:12
相关论文
共 49 条
[1]   Altered expression of E-cadherin in breast cancer:: patterns, mechanisms and clinical significance [J].
Asgeirsson, KS ;
Jónasson, JG ;
Tryggvadóttir, L ;
Olafsdóttir, K ;
Sigurgeirsdóttir, JR ;
Ingvarsson, S ;
Ögmundsdóttir, HM .
EUROPEAN JOURNAL OF CANCER, 2000, 36 (09) :1098-1106
[2]   Tropomyosin-1, a novel suppressor of cellular transformation is downregulated by promoter methylation in cancer cells [J].
Bharadwaj, S ;
Prasad, GL .
CANCER LETTERS, 2002, 183 (02) :205-213
[3]  
BHATTACHARYA B, 1990, CANCER RES, V50, P2105
[4]  
Bissell MJ, 1999, CANCER RES, V59, p1763S
[5]  
Bissell MJ, 1999, CANCER RES, V59, p1757S
[6]   Inhibition of the Arp2/3 complex-nucleated actin polymerization and branch formation by tropomyosin [J].
Blanchoin, L ;
Pollard, TD ;
Hitchcock-DeGregori, SE .
CURRENT BIOLOGY, 2001, 11 (16) :1300-1304
[7]  
Braverman RH, 1996, ONCOGENE, V13, P537
[8]  
Bukholm IK, 1998, J PATHOL, V185, P262, DOI 10.1002/(SICI)1096-9896(199807)185:3<262::AID-PATH97>3.0.CO
[9]  
2-Y
[10]  
Bukholm IK, 2000, J PATHOL, V190, P15