Abstract:
:Progression of breast cancer from an estrogen-dependent, slowly growing tumor amenable to tamoxifen treatment to an aggressive, metastatic, estrogen-independent phenotype has been mimicked by the transfection of MCF-7 breast carcinoma cells with fibroblast growth factors 1 or 4. FGF-transfected cells are aggressively tumorigenic in ovariectomized or tamoxifen-treated nude mice, conditions under which the parental cells would not produce tumors. When detection of metastasis was enhanced by lacZ transfection, the FGF-transfected MCF-7 cells were reliably metastatic to lymph nodes and frequently metastatic to lungs, in further contrast to parental cells. An antiangiogenic drug, AGM-1470, given to mice bearing tumors produced by FGF-transfected MCF-7 cells, produced a decrease in tumor size. The decreased tumor size was not as marked as that produced by treatment with pentosan polysulfate, an agent which would abrogate all autocrine or paracrine effects of the transfected FGF. Thus, increased angiogenesis may be a component of the phenotypic change produced by the FGF transfection, but other autocrine or paracrine effects may also be important. Since a clonal FGF-4 and lacZ doubly-transfected cell line, MKL-4, progressively lost expression of the transfected lacZ gene in individual cells, we performed successive rounds of fluorescence-activated cell sorting to select high-expressing cells. High-expressing cell populations thus obtained rapidly lost expression of beta-gal activity in continued culture. High beta-gal expressing clonal cell lines of MKL-4 cells established by either one or two rounds of low-density cloning also lost lacZ expression with continued culture. Southern analysis of DNA from lacZ transfected cell lines showed the transfected sequences to be present and grossly intact in both high and low expressing populations. However, Northern analysis revealed that high-expressing populations of MKL-4 cells contained the most lacZ mRNA, implying that in the unstable MKL-4 cell line, individual cells are down-regulating mRNA levels of lacZ. Stable lacZ expression has been obtained in other FGF-transfected and parental MCF-7 cell lines using the same expression vector. Thus, the MKL-4 cell line is down-regulating mRNA encoding the transfected gene through a mechanism not dependent on the CMV promotor utilized in the expression vector. This evidence suggests that lacZ expression is not a benign modification in certain cells.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
McLeskey SW,Zhang L,Kharbanda S,Kurebayashi J,Lippman ME,Dickson RB,Kern FGdoi
10.1007/BF01806082subject
Has Abstractpub_date
1996-01-01 00:00:00pages
103-17issue
1eissn
0167-6806issn
1573-7217journal_volume
39pub_type
杂志文章abstract::Old age is associated with comorbidity and decreased functioning which influences treatment decisions in elderly breast cancer patients. The purpose of this study was to identify risk factors for complications after breast cancer surgery in elderly patients, and to assess mortality in patients with postoperative compl...
journal_title:Breast cancer research and treatment
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doi:10.1007/s10549-013-2462-9
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
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abstract::A potential advantage of primary over adjuvant chemotherapy in breast cancer survival had been proposed on theoretical grounds. In 1994, early results of the S6-trial comparing primary chemotherapy vs. adjuvant chemotherapy for operable breast cancer in 390 premenopausal patients had shown significant improvement in s...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Breast cancer research and treatment
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doi:10.1007/s10549-017-4426-y
更新日期:2017-11-01 00:00:00
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journal_title:Breast cancer research and treatment
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doi:10.1023/B:BREA.0000019954.59130.d3
更新日期:2004-04-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806938
更新日期:1982-01-01 00:00:00
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journal_title:Breast cancer research and treatment
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doi:10.1007/BF02633545
更新日期:1991-05-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
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abstract::Several independent studies have presented evidence for the involvement of human papillomaviruses (HPV) in the aetiology of human breast cancer, while others have reported the opposite findings. Here, we have analysed by a high sensitive multiplex PCR-based method the prevalence of alpha mucosal and beta cutaneous HPV...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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更新日期:2009-04-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3946-1
更新日期:2016-09-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2002-05-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析
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更新日期:2013-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s10549-005-5152-4
更新日期:2005-11-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-06054-x
更新日期:2021-01-03 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-4790-2
更新日期:2018-08-01 00:00:00
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
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更新日期:2015-02-01 00:00:00
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journal_title:Breast cancer research and treatment
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更新日期:1987-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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更新日期:1995-07-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-015-3549-2
更新日期:2015-09-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806676
更新日期:1996-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10549-016-3865-1
更新日期:2016-07-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1005822318256
更新日期:1997-09-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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更新日期:2009-05-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05376-9
更新日期:2019-11-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
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更新日期:2014-07-01 00:00:00