Tamoxifen aziridine labeling of the estrogen receptor — potential utility in detecting biologically aggressive breast tumors

Background and aims: Although some preclinical and clinical studies have extensively confirmed the pharmacological effects of the hydroalcoholic extract (HE) of Physalis alkekengi on several diseases, little is known about the effects of P. alkekengi HE (PAHE) on breast cancer. Therefore, this study aimed to investigate the therapeutic effect of PAHE on estrogen receptor+ breast cancer. Methods: To this end, tumors were created in mice by injecting MC4L2 cells into the sternum of the mice. Then, the animals were gavaged for 16 days at 10, 50, and 100 mg/kg daily of PAHE. In addition, the tumor growth and body weight of the mice were measured on the 16th day, and they were killed on 21st day. Finally, their tumor tissues were removed and the apoptotic cell tissue and expression of the ATG-5 gene were studied as well. The experiments were repeated three times, and the data were analyzed using SPSS software (P<0.001 and P<0.05). Results: The average body weight of the control group significantly decreased 16 days after tumor establishment (P<0.001). Further, the PAHE inhibited the growth of the breast cancer tumor in higher doses (50 & 100 mg/kg, P<0.001). Based on the results, a significant histopathological alteration was found in the breast tumors of the PAHE-treated groups compared with the control group, including the decreased level of mitotic cells the intensive level of necrotic cells and lymphocyte infiltration into the breast tumors bearing mice 21 days after PAHE administration (P=0.012). Eventually, PAHE significantly increased the mRNA level of the expression of the autophagy ATG-5 specific gene in the effective dosage-treated group (50 mg/kg, P=0.037). Conclusion: The evidence suggests that the PAHE has a suitable efficacy for the treatment of ER+ breast cancer by promoting autophagy mechanisms into these tumor types

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Magee Equation 3 predicts pathologic response to neoadjuvant systemic chemotherapy in estrogen receptor positive, HER2 negative/equivocal breast tumors

Modern Pathology ◽

10.1038/modpathol.2017.41 ◽

2017 ◽

Vol 30 (8) ◽

pp. 1078-1085 ◽

Cited By ~ 19

Author(s):

Daniel J Farrugia ◽

Alessandra Landmann ◽

Li Zhu ◽

Emilia J Diego ◽

Ronald R Johnson ◽

...

Keyword(s):

Estrogen Receptor ◽

Systemic Chemotherapy ◽

Breast Tumors ◽

Pathologic Response ◽

Estrogen Receptor Positive

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Abstract 2313: Differences in estrogen receptor signaling in normal mammary epithelial cells and ER-positive primary breast tumors and metastases.

10.1158/1538-7445.am2013-2313 ◽

2013 ◽

Author(s):

David Chi ◽

Housheng He ◽

Tony Yeung ◽

Rinath Jeselsohn ◽

Stuart Schnitt ◽

...

Keyword(s):

Estrogen Receptor ◽

Epithelial Cells ◽

Mammary Epithelial Cells ◽

Breast Tumors ◽

Mammary Epithelial ◽

Receptor Signaling ◽

Estrogen Receptor Signaling ◽

Er Positive ◽

Normal Mammary Epithelial

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Estrogen receptor signaling is reprogrammed during breast tumorigenesis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1819155116 ◽

2019 ◽

Vol 116 (23) ◽

pp. 11437-11443 ◽

Cited By ~ 9

Author(s):

David Chi ◽

Hari Singhal ◽

Lewyn Li ◽

Tengfei Xiao ◽

Weihan Liu ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Mammary Gland ◽

Epithelial Cells ◽

Breast Tumors ◽

Normal Mammary Gland ◽

Breast Tumorigenesis ◽

Effective Prevention ◽

Significant Difference ◽

Estrogen Stimulation

Limited knowledge of the changes in estrogen receptor (ER) signaling during the transformation of the normal mammary gland to breast cancer hinders the development of effective prevention and treatment strategies. Differences in estrogen signaling between normal human primary breast epithelial cells and primary breast tumors obtained immediately following surgical excision were explored. Transcriptional profiling of normal ER+ mature luminal mammary epithelial cells and ER+ breast tumors revealed significant difference in the response to estrogen stimulation. Consistent with these differences in gene expression, the normal and tumor ER cistromes were distinct and sufficient to segregate normal breast tissues from breast tumors. The selective enrichment of the DNA binding motif GRHL2 in the breast cancer-specific ER cistrome suggests that it may play a role in the differential function of ER in breast cancer. Depletion of GRHL2 resulted in altered ER binding and differential transcriptional responses to estrogen stimulation. Furthermore, GRHL2 was demonstrated to be essential for estrogen-stimulated proliferation of ER+ breast cancer cells. DLC1 was also identified as an estrogen-induced tumor suppressor in the normal mammary gland with decreased expression in breast cancer. In clinical cohorts, loss of DLC1 and gain of GRHL2 expression are associated with ER+ breast cancer and are independently predictive for worse survival. This study suggests that normal ER signaling is lost and tumor-specific ER signaling is gained during breast tumorigenesis. Unraveling these changes in ER signaling during breast cancer progression should aid the development of more effective prevention strategies and targeted therapeutics.

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Identification of Gene Expression Signature in Estrogen Receptor Positive Breast Carcinoma

Biomarkers in Cancer ◽

10.4137/bic.s3793 ◽

2010 ◽

Vol 2 ◽

pp. BIC.S3793 ◽

Cited By ~ 23

Author(s):

Arvind D. Thakkar ◽

Hemanth Raj ◽

Debarshi Chakrabarti ◽

Ravishankar ◽

N. Saravanan ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Estrogen Receptor ◽

Transcription Factor ◽

Molecular Basis ◽

Clinical Specimen ◽

Gene Expression Signature ◽

Breast Tumors ◽

Significant Group ◽

Six Genes

A significant group of patient with estrogen receptor (ER) α positive breast tumors fails to appreciably respond to endocrine therapy. An increased understanding of the molecular basis of estrogen-mediated signal transduction and resultant gene expression may lead to novel strategies for treating breast cancer. In this study, we sought to identify the dysregulated genes in breast tumors related to ERα status. Microarray analyses of 31 tumor samples showed 108 genes differentially expressed in ERα (+) and ERα (–) primary breast tumors. Further analyses of gene lists indicated that a significant number of dysregulated genes were involved in mRNA transcription and cellular differentiation. The majority of these genes were found to have promoter-binding sites for E74-like factor 5 (ELF5; 54.6% genes), E2F transcription factor 1 (E2F1; 22.2% genes), and nuclear transcription factor Y alpha (NFYA; 32.4% genes). Six candidate genes ( NTN4, SLC7A8, MLPH, ENPP1, LAMB2, and PLAT) with differential expression were selected for further validation studies using RT-qPCR (76 clinical specimen) and immunohistochemistry (48 clinical specimen). Our studies indicate significant overexpression of all the six genes in ERα (+) breast tumors as compared to ERα (–) breast tumors. In vitro studies using T-47D breast cancer cell line confirmed the estrogen dependant expression of four of the above six genes ( SLC7A8, ENPP1, LAMB2, and PLAT). Collectively, our study provides further insights into the molecular basis of estrogen-dependent breast cancer and identifies “candidate biomarkers” that could be useful for predicting endocrine responsiveness.

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