Bcl-2 overexpression enhances the metastatic potential of a human breast cancer line

被引:117
作者
DelBufalo, D [1 ]
Biroccio, A [1 ]
Leonetti, C [1 ]
Zupi, G [1 ]
机构
[1] REGINA ELENA INST CANC RES,EXPT CHEMOTHERAPY LAB,ROME,ITALY
关键词
breast carcinoma; metastases; invasion; migration;
D O I
10.1096/fasebj.11.12.9337147
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bcl-2 protein has been shown to contribute to oncogenesis because it can transform and immortalize cells in cooperation with c-myc, ras, or viral genes, However, in vivo studies have not yet established whether bcl-2 can play a role in metastasis, Here we investigate the potential metastatic role off bcl-2, We introduced the human bcl-2 gene into a low bcl-2 expressing human breast cancer cell line MCF7 ADR, We demonstrate that two bcl-2 overexpressing clones injected intravenously or intramuscularly into nude mice induce a significantly higher number of experimental and spontaneous lung metastases compared to the control transfectant clone, We demonstrate that bcl-2 overexpressing clones are more invasive and migratory in response to chemotactic stimuli than the control transfectant clone, Furthermore, zymographic analysis shows that secretion of 72 and 92 kDa gelatinases increases in the two bcl-2 overexpressing transfectants, Tumors originating from bcl-2 overexpressing clones also show a decrease in the latency period of tumor appearance, In conclusion, our data show that bcl-2 overexpression enhances both tumorigenicity and metastatic potential of MCF7 ADR cells by inducing metastasis-associated properties.
引用
收藏
页码:947 / 953
页数:7
相关论文
共 44 条
  • [1] CHEMOTAXIS OF 3T3 AND SV3T3 CELLS TO FIBRONECTIN IS MEDIATED THROUGH THE CELL-ATTACHMENT SITE IN FIBRONECTIN AND A FIBRONECTIN CELL-SURFACE RECEPTOR
    ALBINI, A
    ALLAVENA, G
    MELCHIORI, A
    GIANCOTTI, F
    RICHTER, H
    COMOGLIO, PM
    PARODI, S
    MARTIN, GR
    TARONE, G
    [J]. JOURNAL OF CELL BIOLOGY, 1987, 105 (04) : 1867 - 1872
  • [2] ALBINI A, 1987, CANCER RES, V47, P3239
  • [3] MOLECULAR THEMES IN ONCOGENESIS
    BISHOP, JM
    [J]. CELL, 1991, 64 (02) : 235 - 248
  • [4] CAMPOS L, 1993, BLOOD, V81, P3091
  • [5] CHAN WK, 1993, J PATHOL S, V169, P138
  • [6] CHAOYING Y, 1997, NATURE, V385, P637
  • [7] COLOMBEL M, 1993, AM J PATHOL, V143, P390
  • [8] DAWSON CW, 1995, ONCOGENE, V10, P69
  • [9] Lonidamine induces apoptosis in drug-resistant cells independently of the p53 gene
    DelBufalo, D
    Biroccio, A
    Soddu, S
    Laudonio, N
    DAngelo, C
    Sacchi, A
    Zupi, G
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1996, 98 (05) : 1165 - 1173
  • [10] COOPERATIVE INTERACTION BETWEEN C-MYC AND BCL-2 PROTOONCOGENES
    FANIDI, A
    HARRINGTON, EA
    EVAN, GI
    [J]. NATURE, 1992, 359 (6395) : 554 - 556