SUM-159PT cells: a novel estrogen independent human breast cancer model system

Flanagan, Louise; Weelden, K Van; Ammerman, Cheryl A.; Ethier, Stephen P.; Welsh, JoEllen

doi:10.1023/a:1006331716981

Cited by 67 publications

(56 citation statements)

References 20 publications

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“…p,p´-DDA, unlike the DDT, DDD, and DDE isoforms, possesses no central chlorines but only a carboxylic acid motif, suggesting the chlorine residues are necessary. Vehicle + PMA (%) Often, late-stage endocrine cancers grow in the absence of hormones (80)(81)(82), indicating the potential up-regulation of some other cell survival/cell signaling mechanisms. Because our estrogen-unresponsive cells give a stronger AP-1 activation, it is possible that the AP-1 signaling mechanisms have been up-regulated to compensate for the loss of responsiveness to estrogen.…”

Section: Discussionmentioning

confidence: 99%

DDT and its metabolites alter gene expression in human uterine cell lines through estrogen receptor-independent mechanisms.

Frigo

Burow

Mitchell

et al. 2002

Environ Health Perspect

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Endocrine-disrupting organochlorines, such as the pesticide dichlorodiphenyltrichloroethane (DDT), bind to and activate estrogen receptors (ERs), thereby eliciting estrogen-like effects. Although ERs function predominantly through activation of transcription via estrogen-responsive elements, both ERs, alpha and ss, can interact with various transcription factors such as activator protein-1 (AP-1). Additionally, estrogens may regulate early signaling events, suggesting that the biological effects of environmental estrogens may not be mediated through classic ER (alpha and ss) activity alone. We hypothesized that known environmental estrogens, such as DDT and its metabolites, activate AP-1-mediated gene transactivation through both ER-dependent and ER-independent means. Using two Ishikawa human endometrial adenocarcinoma cell line variants that we confirmed to be estrogen responsive [Ishikawa(+)] and estrogen unresponsive [Ishikawa(-)], we generated stably transfected AP-1 luciferase cell lines to identify the role of an estrogen-responsive mechanism in AP-1-mediated gene expression by various stimuli. Our results demonstrate that DDT and dichlorodiphenyldichloroethane (DDD) were the most potent activators of AP-1 activity; 2,2-bis(p-chlorophenyl) acetic acid failed to activate. Although stimulated in both Ishikawa(+) and Ishikawa(-) cells by DDT and its congeners, AP-1 activation was more pronounced in the estrogen-unresponsive Ishikawa(-) cells. In addition, DDT, DDD, and dichlorodiphenyldichloroethylene (DDE) could also stimulate AP-1 activity in the estrogen-unresponsive human embryonic kidney 293 cells using a different promoter context. Thus, our data demonstrate that DDT and its metabolites activate the AP-1 transcription factor independent of ER (alpha or ss) status.

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Section: Discussionmentioning

confidence: 99%

DDT and its metabolites alter gene expression in human uterine cell lines through estrogen receptor-independent mechanisms.

Frigo

Burow

Mitchell

et al. 2002

Environ Health Perspect

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“…The estrogen-independent breast cancer cell line SUM-159-PT has been described (40) and was maintained in Ham's F-12 medium with L-glutamine (Cambrex, Walkersville, MD) supplemented with 5% fetal bovine serum, 1 g/ml hydrocortisone, and 5 g/ml insulin (Sigma). SUM.N1-16 and 435.N1-23 cells with inducible NFAT1 expression were derived from SUM-159-PT and MDA-MB-435 cells, respectively, and generated using the tetracycline-regulated expression system from Invitrogen.…”

Section: Methodsmentioning

confidence: 99%

NFAT Induces Breast Cancer Cell Invasion by Promoting the Induction of Cyclooxygenase-2

Yiu

Toker

2006

Journal of Biological Chemistry

141

135

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The NFAT (nuclear factor of activated T cells) family of transcription factors plays a fundamental role in the transcriptional regulation of the immune response. However, NFATs are ubiquitously expressed, and recent evidence points to their important functions in human epithelial cells and carcinomas. Specifically, NFAT has been shown to be active in human breast and colon carcinoma cells and to promote their invasion through Matrigel. The mechanisms by which NFAT promotes invasion have not been defined. To identify NFAT target genes that induce carcinoma invasion, we have established stable breast cancer cell lines that inducibly express transcriptionally active NFAT. Gene expression profiling by cDNA microarray of cells induced to express NFAT revealed up-regulation of cyclooxygenase-2 (COX-2). Increased NFAT expression and activity induced COX-2 expression as well as prostaglandin E 2 synthesis. This induction was more prominent when NFAT was activated by phorbol 12-myristate 13-acetate and calcium ionophore ionomycin and was blocked by the NFAT antagonist cyclosporin A. Breast cancer cells with elevated COX-2 expression showed increased invasion through Matrigel, and this was reduced in cells treated with COX-2 inhibitors. Conversely, loss of NFAT1 protein expression using small interfering RNA led to a reduction in COX-2 transcription and reduced invasion. Similarly, Matrigel invasion was reduced in cells in which COX-2 expression was reduced using specific siRNA. These findings demonstrate that NFAT promotes breast cancer cell invasion through the induction of COX-2 and the synthesis of prostaglandins.

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“…To assess the putative functional dependence of Met on the ␣ 6 ␤ 4 integrin from a different perspective, we used SUM-159 cells (22). These invasive breast carcinoma cells express both ␣ 6 ␤ 4 and Met (Fig.…”

Section: Integrin Has a Generic Influence On Carcinoma Invasion That mentioning

confidence: 99%

“…The potential significance of these results prompted us to re-examine the central findings of this study, which were that a selective physical association between Met and ␣ 6 ␤ 4 exists on the surface of invasive carcinoma cells and that Met cannot promote invasion in the absence of ␣ 6 ␤ 4 expression. g/ml insulin, 1 mg/ml hydrocortisol, 1% penicillin-streptomycin, and 25 mM Hepes (22).…”

mentioning

confidence: 99%

The Met Receptor and α6β4 Integrin Can Function Independently to Promote Carcinoma Invasion

Chung

Yoon

Lipscomb

et al. 2004

Journal of Biological Chemistry

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It has been proposed that a constitutive, physical association of the Met receptor and the ␣ 6 ␤ 4 integrin exists on the surface of invasive carcinoma cells and that hepatocyte growth factor (HGF)-mediated invasion is dependent on ␣ 6 ␤ 4 (Trusolino, L., Bertotti, A., and Comoglio, P. M. (2001) Cell 107, 643-654). The potential significance of these results prompted us to re-examine this hypothesis. Using three different carcinoma cell lines that express both Met and ␣ 6 ␤ 4 , we were unable to detect the constitutive association of these receptors by co-immunoprecipitation. Moreover, carcinoma cells that lacked expression of ␣ 6 ␤ 4 exhibited Met-dependent invasion toward HGF, and increasing Met expression by viral infection of these cells enhanced invasion without inducing ␣ 6 ␤ 4 expression. Although expression of ␣ 6 ␤ 4 in such cells enhanced their invasion to HGF, it also enhanced their ability to invade toward other chemoattractants such as lysophosphatidic acid, and this latter invasion was not inhibited by a function-blocking Met antibody. Finally, depletion of ␤ 4 by RNA interference in invasive carcinoma cells that express both receptors reduced the ability of these cells to invade toward HGF by ϳ25%, but it did not abrogate their invasion. These data argue that the invasive function of Met can be independent of ␣ 6 ␤ 4 and that ␣ 6 ␤ 4 has a generic influence on the invasion of carcinoma cells that is not specific to Met.Understanding the receptor-mediated mechanisms that underlie invasive carcinoma is a timely and significant endeavor. The involvement of specific integrins and growth factor receptors in the invasive process is established, and several lines of evidence indicate that these two classes of surface receptors may cooperate to effect a wide range of biological functions, including the migration and invasion of tumor cells (2-4). The available data indicate that integrin and growth factor signaling can be synergistic, and in some cases physical association may occur between these receptor types. Insight into the nature of such receptor interactions has important implications not only for understanding the biology of tumor invasion but also for the design and use of therapeutics targeted to these receptors (5).

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SUM-159PT cells: a novel estrogen independent human breast cancer model system

Cited by 67 publications

References 20 publications

DDT and its metabolites alter gene expression in human uterine cell lines through estrogen receptor-independent mechanisms.

DDT and its metabolites alter gene expression in human uterine cell lines through estrogen receptor-independent mechanisms.

NFAT Induces Breast Cancer Cell Invasion by Promoting the Induction of Cyclooxygenase-2

The Met Receptor and α6β4 Integrin Can Function Independently to Promote Carcinoma Invasion

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