Prostate-Derived ETS Factor Is a Mediator of Metastatic Potential through the Inhibition of Migration and Invasion in Breast Cancer

Turner, David P.; Moussa, Omar; Sauane, Moira; Fisher, Paul B.; Watson, Dennis K.

doi:10.1158/0008-5472.can-06-2913

Cited by 65 publications

(95 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A Tet-On prostate cancer cell line was used (19) and PDEF expression was routinely induced by using doxycycline (DOX) (RPI, Inc.) at a concentration of 1 µg for 24 h in PC3 cells. This system can induce activation of target gene (i.e., PDEF in our study) in a stringent, reversible, specific manner to study underlying biological and pathological processes (25).…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

“…In order to gain insight into the function of PDEF, in the present study we used isobaric tags for relative and absolute quantitation (iTRAQ)-labeling coupled with mass spectrometry (MS) to identify differentially expressed proteins upon PDEF induction using a Tet-On system in prostate cancer cells (19). This study is the first to report the use of iTRAQ labeling MS to identify differentially expressed proteins upon PDEF induction and validate the results with in vitro functional assays (20,21).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PDEF downregulates stathmin expression in prostate cancer

et al. 2012

View full text Add to dashboard Cite

Abstract. The Ets proteins are a family of transcription factors characterized by an evolutionarily conserved DNA binding domain that controls key cellular processes. Prostate-derived Ets transcription factor (PDEF), a member of the Ets family, is reported to be present in tissues with high epithelial content, notably breast and prostate. However, the role of PDEF in cancer development is not fully understood. To gain insight into the molecular mechanisms associated with prostate cancer progression, we employed iTRAQ labeling followed by mass spectrometric (MS) analysis to identify candidate proteins that are differentially expressed in prostate cancer cells with or without PDEF. To this end, we overexpressed PDEF in PC3 human prostate cells using a tetracycline inducible system (Tet-On). Many differentially expressed proteins which play important roles in various cellular and biological processes were identified. Among them, stathmin (STMN), which is a microtubule (MT)-destabilizing protein, was found to be downregulated in multiple analyses. We demonstrated that re-expression of STMN reversed the antitumor properties of PDEF in PDEF-overexpressing PC3 cells. Using in vitro functional assays, we showed that STMN overexpression counteracted PDEF's effects against cell proliferation, colony formation and tumor migration. Similar results were further confirmed with the prostate cancer cell line CWR22rv1. In conclusion, many differentially expressed proteins were identified and STMN was found to be downregulated by PDEF.These results suggest that PDEF may inhibit prostate cancer progression by transcriptional downregulation of oncogenic STMN expression. Analyzing the association among differentially expressed proteins may provide a basis to better understand the molecular mechanisms underlying the process of cancer progression and development and further aid in designing therapeutics in the future. IntroductionProstate cancer is the most common cancer diagnosed among men and the second leading cause of death in American men, behind only lung cancer. The American Cancer Society (ACS) estimates about 1 man in 36 will die of prostate cancer (1). Although screening for prostate cancer, based on prostate specific antigen (PSA) has revolutionized early detection and diagnosis of the disease, the challenge that clinicians face are to determine which patients progress to aggressive disease (2,3). In order to determine the possibility of disease progression and ability to manage patient outcomes, it is necessary to better understand the molecular processes underlying the disease development and progression. Gene regulation is an important process in maintaining the integrity of cells for their proper growth and survival. Improper regulation of genes can lead to various diseases like cancer. The Ets family of transcription factors has been long investigated for their role in genetic loss of cellular homeostasis which results in development of various cancers. So far, 25 human and 26 murine Ets family members have been report...

show abstract

Section: Chemicals and Reagentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PDEF downregulates stathmin expression in prostate cancer

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Rather, these luminal epithelial specific transcription factors may reduce the mesenchymal phenotype of these cell lines, rendering them less invasive and less migratory. 17,23 Indeed, classically, pre-malignant cell lines such as NIH 3T3 cells were used in transfection experiments to determine the transforming capacity of putative cancer genes. Similarly, the individual genes described in the review article 24 to ascribe a potential tumor suppressor role for PDEF were mostly derived from the studies that transfected PDEF into malignant tumor cell lines.…”

Section: Pdef An Oncogenic Driver Of Breast Cancermentioning

confidence: 99%

Prostate-derived Ets factor, an oncogenic driver in breast cancer

2017

View full text Add to dashboard Cite

Prostate-derived Ets factor (PDEF), a member of the Ets family of transcription factors, differs from other family members in its restricted expression in normal tissues and its unique DNA-binding motif. These interesting attributes coupled with its aberrant expression in cancer have rendered PDEF a focus of increasing interest by tumor biologists. This review provides a current understanding of the characteristics of PDEF expression and its role in breast cancer. The bulk of the evidence is consistent with PDEF overexpression in most breast tumors and an oncogenic role for this transcription factor in breast cancer. In addition, high PDEF expression in estrogen receptor-positive breast tumors showed significant correlation with poor overall survival in several independent cohorts of breast cancer patients. Together, these findings demonstrate PDEF to be an oncogenic driver of breast cancer and a biomarker of poor prognosis in this cancer. Based on this understanding and the limited expression of PDEF in normal human tissues, the development of PDEF-based therapeutics for prevention and treatment of breast cancer is also discussed. KeywordsProstate-derived Ets factor, Sam-pointed domain containing Ets transcription factor, oncogenic driver in breast cancer, biomarker in breast cancer Date

show abstract

“…This is mediated through the increased expression of genes including, but not limited to, BCL2, inhibitor of apoptosis (IAP's) family members, matrixmetalloproteinases (MMP's), urokinase plasminogen activator (uPA), and vimentin and the downregulation of Ecadherin [14,21]. PDEF is an epithelial specific ETS family member and in contrast to ETS1 is associated with the negative regulation of metastatic potential [22][23][24][25][26]. Although PDEF message is sometimes found to be expressed in primary prostate and breast cancer and has been proposed as a prognostic marker [27], our research has recently identified post-translational regulation by microRNA's as a mechanism of PDEF protein loss during tumorogenesis in both tissues [28] (manuscript in prep).…”

Section: Ets Transcription Factors and Cancermentioning

confidence: 99%

“…Although PDEF message is sometimes found to be expressed in primary prostate and breast cancer and has been proposed as a prognostic marker [27], our research has recently identified post-translational regulation by microRNA's as a mechanism of PDEF protein loss during tumorogenesis in both tissues [28] (manuscript in prep). Increased PDEF expression in metastatic prostate and breast cell lines is associated with decreased metastatic potential through the inhibition of cell growth, migration and invasion [22,[24][25][26] through the decreased expression of cancer-associated genes such as uPA [25], survivin [23], vimentin, and SNAI2 [24] as well as the increased expression of Maspin [22] and E-cadherin [24]. Similarly to prostate, studies demonstrate that PDEF protein is expressed in normal breast tissue, but reduced in welldifferentiated ductal carcinoma and lost in poorly differentiated ductal carcinoma [29].…”

Section: Ets Transcription Factors and Cancermentioning

confidence: 99%

The Role of ETS Transcriptional Regulation in Hormone Sensitive and Refractory Prostate Cancer

Turner¹

2010

TOCJ

Self Cite

View full text Add to dashboard Cite

Most advanced prostate tumors are dependent upon hormonal regulation of the transcriptional activity of the androgen receptor (AR). Current ASCO recommendations for initial treatment of advanced disease target the hormonal mediated regulation of AR activation through androgen deprivation therapy. Despite early treatment efficacy, most prostate tumors progress and re-activate AR transcriptional regulation through alternative biological mechanisms that allow them to circumvent the requirement for androgen. It is the temporal and spatial recruitment of specific AR transcriptional complexes to the promoters of cancer associated target genes that promotes the tumorigenic phenotype in prostate cancer. Increasing published data associates the E Twenty Six (ETS) family of transcription factors with prostate cancer progression and with the transcriptional activity of the AR. Evidence suggests that ETS factors act in concert to both positively and negatively regulate the pathways that control progression to metastatic cancer in prostate tissues. Given the critical roles both ETS factors and the AR play in the development of prostate cancer, mechanistic insight into their transcriptional co-regulation during the hormone sensitive and hormone refractory phases of progression will be provided by determining the contribution of ETS, AR and ETS-AR mediated regulatory control. This review examines the current depth of understanding of the role of the ETS family of transcription factors as transcriptional elements that confer the carcinogenic response to aberrant hormonal activity during prostate cancer progression.

show abstract

Prostate-Derived ETS Factor Is a Mediator of Metastatic Potential through the Inhibition of Migration and Invasion in Breast Cancer

Cited by 65 publications

References 39 publications

PDEF downregulates stathmin expression in prostate cancer

PDEF downregulates stathmin expression in prostate cancer

Prostate-derived Ets factor, an oncogenic driver in breast cancer

The Role of ETS Transcriptional Regulation in Hormone Sensitive and Refractory Prostate Cancer

Contact Info

Product

Resources

About