Ets2-dependent microenvironmental support of mouse mammary tumors

Tynan, John A.; Wen, Fang; Muller, William J.; Oshima, Robert G.

doi:10.1038/sj.onc.1208856

Cited by 23 publications

(24 citation statements)

References 15 publications

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“…While mammary tumor development was not influenced by Ets2 deficiency in epithelial cells, nearly complete loss of Ets2 in the adult mouse was associated with a delay of tumor onset. As noted with constitutive Ets2 deletion, once tumors appeared, their rate of growth was not significantly altered by ubiquitious deletion [109]. These observations support the notion that stromal Ets2 expression regulates the initiation and progression of mammary epithelial tumor development.…”

Section: Ets2supporting

confidence: 75%

ETS Transcription Factor Expression and Conversion During Prostate and Breast Cancer Progression

Watson¹,

Turner²,

Scheiber³

et al. 2010

TOCJ

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ETS factors are known to act as positive or negative regulators of the expression of genes including those that control response to various signaling cascades, cellular proliferation, differentiation, hematopoiesis, apoptosis, adhesion, migration, invasion and metastasis, tissue remodeling, ECM composition and angiogenesis. During cancer progression, altered ETS gene expression disrupts the regulated control of many of these biological processes. Although it was originally observed that specific ETS factors function either as positive or negative regulators of transcription, it is now evident that the same ETS factor may function in reciprocal fashions, reflecting promoter and cell context specificities. This report will present a discussion of ETS factor expression during prostate and breast cancer progression and its functional roles in epithelial cell phenotypes.The ETS genes encode transcription factors that have independent activities but are likely to be part of an integrated network. While previous studies have focused on single ETS factors in the context of specific promoters, future studies should consider the functional impact of multiple ETS present within a specific cell type. The pattern of ETS expression within a single tissue is, not surprisingly, quite complex. Multiple ETS factors may be able to regulate the same genes, albeit at different magnitude or in different directions. Furthermore, the precise balance between cancer promotion and inhibition by ETS factors, which may differentially regulate specific target genes, can thus control its progression. These concepts form the basis of the hypothesis that "Ets conversion" plays a critical role during tumor progression. Examples supporting this hypothesis will be described.Keywords: ETS, transcription, prostate cancer, breast cancer, cancer progression, biological control. ETS GENE FAMILYThe oncogene v-ets was first characterized in 1983 as part of the transforming fusion protein of an avian retrovirus, E26 (ets, E26 transforming sequence). Subsequent identification of v-ets related genes from metazoan species established the Ets family as one of the largest families of transcriptional regulators, with diverse functions and activities (for reviews, see [1][2][3][4] and references therein). To date, 27 human ETS family members have been identified (Fig. (1) and Table 1). All Ets genes retain a conserved winged helixturn-helix DNA binding domain (the ETS domain) of ~ 85 amino acids that recognizes a core GGAA/T sequence (ETS binding site, EBS). ETS proteins, with the exception of GABPα, bind DNA as monomers. The second conserved domain found in a subset of ETS genes is the pointed (PNT) domain. This 65-85 amino acid domain is found in 11 of 27 human ETS genes and has been shown to function in protein-protein interaction and oligomerization. ETS factors have been classified into 12 subgroups based upon Ets domain sequence homology: ETS, ERG, PEA3, ETV2, TCF, GABP, ELF, SPI, TEL, ERF, PDEF and ESE [2, 5] (See Table 1 for subgroup members). ...

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Section: Ets2supporting

confidence: 75%

ETS Transcription Factor Expression and Conversion During Prostate and Breast Cancer Progression

Watson¹,

Turner²,

Scheiber³

et al. 2010

TOCJ

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“…The im portance of the Pten-Ets2 axis in stom al fibroblasts is consistent with previous wo rk from Oshima and colleag ues that sho wed a critical cell non-autonomous role for Ets2 in m ammary tumor growth ( Tynan et al 2005). Moreover, analysis of tumor-stroma gene expression signatures identified Ets2 activation as a key event associated with breast cancer patients having the worst prognosis .…”

Section: Discussionsupporting

confidence: 75%

Role of PTEN in the Tumor Microenvironment

Leone¹

2009

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information , 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY) 2009 REPORT TYPE Annual DATES COVERED (From -To) TITLE AND SUBTITLE Role of PTEN in the Tumor Microenvironment 5a. CONTRACT NUMBERW81XWH-07-1-0402 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER AUTHOR(S)Gustavo Leone, Ph.D.5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)The Ohio State University Research Foundation PERFORMING ORGANIZATION REPORT NUMBERColumbus, Oh 43210 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Reseaarch and Materiel Command Fort Detrick, Maryland 21702 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release SUPPLEMENTARY NOTES ABSTRACTRecent scientific advances have revealed that a malignant tumor can be viewed as an org an consisting of d ifferent types of interacting cells. Different tumor cell types play different roles in the growth and development of the tumor and thus in the end, all cells within the tumor may help pave the way for further tumor growth in a patient with cancer. Current work in the field indicates that fibroblasts surrounding breast cancers are particularly important for cancer progression, but no on e knows why . O ur experimental approach to this problem is a direct one; we target the mutation of genes in stromal fibroblasts surrounding the tumor in order to learn whether these genes are important for cancer progression. Using this approach we have shown that the Pten gene in fibroblasts is a major gen e involved in suppressing epithelial breast cancers. In order to understand how Pten works in fibroblasts we will measure the im mediate and long-term consequences of Pten mu tation on th e biolog y of all the cells su rrounding the tumor, in cluding th e tumo r cells themselves, as well as the matrix that holds these cells together. Because the entire system is so complex, we plan to study how the Pten gene behaves as a tumor suppres sor b y d eveloping ex tremely d etailed three-dimensional images of tumors wher e each image is annotated with detailed c ancer related molecular infor mation. This will allow us to u se bioinfor...

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“…Pathological characterization showed that the absence of Ets2 in fibroblasts caused reduced epithelial tumor cell proliferation and delayed tumor progression. We also confirmed the results of Oshima's group [31], finding that deletion of Ets2 in the mammary epithelial cells had no effect on tumor growth or progression (F.L. and M.C.O., manuscript in preparation).…”

Section: The Pten/ets2 Axis In Tumor Fibroblastssupporting

confidence: 78%

“…Analysis of tumors from Ets2 A72/A72 mice suggested that lower production of extracellular matrix proteases like MMP9 correlated with lower ETS2 activity [30]. In a follow up study, this group specifically knocked out Ets2 in PyMT mammary tumor cells using a loxP conditional allele of Ets2 and MMTV-Cre, and found this deletion had no effect on tumor initiation [31]. In contrast, generalized conditional knockout of Ets2 using Mox2-Cre (MORE) also resulted in lower tumor growth.…”

Section: Ets Factors In Cancer Stromamentioning

confidence: 99%

ETS Transcription Factors in the Tumor Microenvironment

Li¹,

Wallace²,

Ostrowski³

2010

TOCJ

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ETS factors are involved in cancer progression through transcriptional regulation of factors mediating cell cycle, cell growth, apoptosis, cell adhesion and migration. The biological processes regulated by ETS factors are important not only in tumor cells, but also in the surrounding cells comprising the tumor microenvironment. Additionally, ETS factors can serve as transcriptional activators and repressors to regulate gene expression in a cell context-specific fashion. Here we discuss recent advances in which the regulatory roles of ETS factors in stromal cells are critical during both development and cancer. These new findings uncover the importance of ETS signaling in the stromal compartment of tumors and shed light on new potential mechanisms of ETS factors.

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Ets2-dependent microenvironmental support of mouse mammary tumors

Cited by 23 publications

References 15 publications

ETS Transcription Factor Expression and Conversion During Prostate and Breast Cancer Progression

ETS Transcription Factor Expression and Conversion During Prostate and Breast Cancer Progression

Role of PTEN in the Tumor Microenvironment

ETS Transcription Factors in the Tumor Microenvironment

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