Clinicopathologic and Prognostic Significance of Transducin-Like Enhancer of Split 1 Protein Expression in Invasive Breast Cancer

Lee, Ji Hye; Bae, Sang Byung; Oh, Mee‐Hye; Cho, Hyun Deuk; Jang, Si Hyong; Hong, Soon Auck; Cho, Junhun; Kim, Sung Yong; Han, Sun Wook; Lee, Jong Eun; Kim, Hee Jin; Lee, Hyun Ju

doi:10.4048/jbc.2017.20.1.45

Cited by 10 publications

(7 citation statements)

References 25 publications

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“…In invasive breast cancer, TLE1 was shown to be significantly associated with the human epidermal growth factor receptor 2+ and triple-negative breast cancer subtypes. However, this study did not find a significant association between TLE1 expression and disease-free survival (DFS) or overall survival (OS) (32).…”

Section: Discussioncontrasting

confidence: 83%

Transducin-Like Enhancer of Split-1 Inhibits Malignant Behaviors in vitro and Predicts a Better Prognosis in Pancreatic Ductal Adenocarcinoma

et al. 2020

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Background: Transducin-like enhancer of split-1 (TLE1), a member of the Groucho/TLE family of transcriptional corepressors, has been reported to be involved in the tumorigenesis of various cancers and function as a clinical prognostic indicator. However, the mechanisms and prognostic significance of TLE1 in pancreatic ductal adenocarcinoma (PDAC) have not been elucidated. Methods: In this study, western blot analyses and real-time polymerase chain reaction (RT-PCR) were employed to evaluate the expression of TLE1 and related proteins in PDAC cell lines. Wound healing, transwell migration and invasion, and Cell Counting Kit-8 (CCK-8) assays were used to determine cell line-specific differences in metastasis and proliferation. Flow cytometry was performed for cell cycle detection. RNA sequencing and bioinformatics were undertaken to explore the molecular mechanisms and potential targeted molecules of TLE1. TLE1 expression in tumor and para-tumor tissues was evaluated by tissue microarray-based immunohistochemistry using a semiquantitative method (H-score) in 262 patients with radical PDAC resection. Correlation, Kaplan-Meier survival, univariate, and multivariate analyses were also performed. Results: Our findings showed that TLE1 expression was common in PDAC cell lines. Upregulation of TLE1 inhibited PDAC cell migration, invasion, and proliferation in vitro by delaying the G0/G1 transition. Immunohistochemistry revealed that TLE1 was specifically expressed in the nucleus and at higher levels in tumor tissues compared with para-tumor tissues. Generally, high TLE1 expression was associated with no vascular invasion. In univariate analyses, high TLE1 expression was associated with longer disease-specific survival (DSS) in all patients and in 16 patient subgroups. In multivariate analyses, TLE1 expression was independently associated with DSS in all patients and four patient subgroups. Wang et al. TLE1 and Pancreatic Ductal Adenocarcinoma Conclusion: In conclusion, these results suggest that TLE1 has an inhibitory role in PDAC progression and is a favorable prognostic indicator for patients with resectable PDAC.

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Section: Discussioncontrasting

confidence: 83%

Transducin-Like Enhancer of Split-1 Inhibits Malignant Behaviors in vitro and Predicts a Better Prognosis in Pancreatic Ductal Adenocarcinoma

et al. 2020

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“…1,[4][5][6][7][8]12 Additionally, TLE1 expression has recently been identified in invasive breast cancer with high expression significantly associated with HER2 positivity. 13 Furthermore, certain populations of normal cells are variably labeled by TLE1, including endothelium, mesothelium, perineurium, basal keratinocytes, and adipocytes. 7 Indeed, in the present study, TLE1 was noted to also highlight sebaceous glands and follicular epithelium.…”

Section: Discussionmentioning

confidence: 99%

Expression of TLE1 in Malignant Melanoma With Spindle Cell Morphology: A Potential Diagnostic Pitfall

et al. 2018

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Objectives. Transducer-like enhancer of split 1 (TLE1) immunohistochemistry is widely used as a biomarker of synovial sarcoma. Spindle cell or desmoplastic melanoma can morphologically mimic synovial sarcoma. The aim of this study was to investigate the expression of TLE1 in melanomas with a spindle cell morphology. Methods. A search of the surgical pathology files resulted in 57 cases of melanomas diagnosed with a spindle cell or desmoplastic component. After review, 8 cases had no definitive dermal spindle cell component and 7 cases had insufficient tissue remaining and were excluded from the study. A total of 42 melanomas were examined for TLE1 immunohistochemistry using a mouse monoclonal antibody (Cell Marque, clone 1F5). Strength and percentage of nuclear TLE1 positivity was graded on a scale from 0 to 3+. Staining for TLE1 was considered positive for 2 to 3+ and negative for 0 to 1+. Results. Nuclear TLE1 expression was identified in 24 (57%) of the 42 melanoma cases with spindle cell morphology (2+, n = 14; 3+, n = 10). TLE1 was considered negative in 18 cases (43%), of which most contained weak staining (1+, n = 14 [33%]) and only a small subset did not show any staining (0, n = 4 [10%]). Conclusion. TLE1 frequently highlights melanomas with spindle cell morphology and is a potential diagnostic pitfall. Therefore, when evaluating spindle cell tumors in which the differential may include both a melanoma and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an immunohistochemical panel.

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“…A well-established recent characterization study of PBX1 identified its importance as a valuable prognostic biomarker in BC. Defining signatures in chromatin facilitators involved in cancer characterized some of the pioneer factors like the GATA family of proteins, TLE1 protein, and PBX1 as a valuable prognostic biomarker in BC [68][69][70]. With the advent of newer technologies in genomics and proteomics, novel ER-associated pioneer factors have been continuously identified.…”

Section: Therapeutic Significance Of Targeting Er-associated Pioneer mentioning

confidence: 99%

Emerging role of pioneer transcription factors in targeted ERα positive breast cancer

Pavithran

Kumavath

2021

Exploration of Targeted Anti-Tumor Therapy

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Transcription factors (TFs) are modular protein groups that preferably bind to DNA sequences and guide genomic expression through transcription. Among these key regulators, “pioneer factors” are an emerging class of TFs that specifically interact with nucleosomal DNA and facilitate accessible genomic binding sites for the additional TFs. There is growing evidence of these specialized modulators in particular malignancies, as highlighted by agents’ clinical efficacy, specifically targeting nuclear hormone receptors. They have been implicated in multiple cancers more recently, with a high proportion inculpating on hormone influential cancers. Moreover, extended crosstalk and cooperation between ERα pioneering factors in estrogen-dependent breast cancer (BC) remain elucidated. This review discusses on the recent advances in our understanding of pioneer TFs in cancer, especially highlighting its potentiality to modulate chromatin condensation to permit ERα recruitment in BC cells. Through the study it was concluded that the highly prospected pioneer TFs in BC, including FOXA1, TLE1, PBX1, and GATA3, possess the potential therapeutic significance and further innovations in the field could yield targeted therapy in cancer treatment.

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Clinicopathologic and Prognostic Significance of Transducin-Like Enhancer of Split 1 Protein Expression in Invasive Breast Cancer

Cited by 10 publications

References 25 publications

Transducin-Like Enhancer of Split-1 Inhibits Malignant Behaviors in vitro and Predicts a Better Prognosis in Pancreatic Ductal Adenocarcinoma

Transducin-Like Enhancer of Split-1 Inhibits Malignant Behaviors in vitro and Predicts a Better Prognosis in Pancreatic Ductal Adenocarcinoma

Expression of TLE1 in Malignant Melanoma With Spindle Cell Morphology: A Potential Diagnostic Pitfall

Emerging role of pioneer transcription factors in targeted ERα positive breast cancer

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