TRPS1 Confers Multidrug Resistance of Breast Cancer Cells by Regulating BCRP Expression

Hu, Jing; Zhang, Hui; Liu, Long; Han, Bo; Zhou, Guangjun; Su, Peng

doi:10.3389/fonc.2020.00934

Cited by 9 publications

(8 citation statements)

References 43 publications

(49 reference statements)

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“…This sensitivity is comparable to that seen in most breast carcinomas, where TRPS1 is expressed in > 95% of lobular, triple‐negative, metaplastic and metastatic breast carcinoma 13 . Notably, hormonally active ductal carcinomas of the breast are TRPS1‐positive in only ~50% of cases 14 …”

Section: Discussionsupporting

confidence: 53%

“…13 Notably, hormonally active ductal carcinomas of the breast are TRPS1-positive in only ~50% of cases. 14 Although the number of cases in this study is limited due to their rarity, the most useful finding is that TRPS1 appears to be highly specific for EMPD, as all evaluated melanoma in situ (n = five), urothelial carcinoma (n = one) and anorectal adenocarcinomas with pagetoid spread in the anal skin (n = two) are TRPS1-negative. The distinction of primary EMPD and secondary urothelial carcinoma in the vulva is another potential use for TRPS1, as there are few biomarkers (i.e.…”

Section: Discussionmentioning

confidence: 82%

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TRPS1 expression is sensitive and specific for primary extramammary Paget disease

2023

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Aims: Extramammary Paget disease (EMPD) is an epithelial neoplasm that can occur at many sites, including the vulva and scrotum. EMPD is characterised by the presence of neoplastic cells, in single cells and clusters, that infiltrate all layers of nonneoplastic squamous epithelium. The differential diagnosis for EMPD includes melanoma in situ and secondary involvement of tumours from other sites, such as urothelial or cervical; pagetoid spread of tumor cells can also been seen at other sites, such as anorectal mucosa. The most frequently utilised biomarkers for confirming the diagnosis of EMPD include CK7 and GATA3; however, these biomarkers lack specificity. The purpose of this study was to evaluate TRPS1, a newly described breast biomarker, in pagetoid neoplasms of the vulva, scrotum and anorectum.Methods and results: Fifteen cases of primary EMPD of the vulva (two with associated invasive carcinoma) and four primary EMPD of the scrotum showed strong nuclear immunoreactivity for TRPS1. In contrast, five cases of vulvar melanoma in situ, one case of urothelial carcinoma with secondary pagetoid spread into the vulva and two anorectal adenocarcinomas with pagetoid spread into anal skin (one with associated invasive carcinoma) were negative for TRPS1. Additionally, weak nuclear TRPS1 staining was observed in nonneoplastic tissues (e.g. keratinocytes), but always with less intensity when compared to tumour cells. Conclusions: These results demonstrate that TRPS1 is a sensitive and specific biomarker for EMPD, and may be especially useful for excluding secondary involvement of the vulva by urothelial and anorectal carcinomas.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 82%

TRPS1 expression is sensitive and specific for primary extramammary Paget disease

2023

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“…A recent study by Hu et al 25 reported that overexpression of TRPS1 has led to upregulation of breast carcinoma resistant protein (BCRP), a protein that plays an important role in the development of multi‐drug resistance which is a major hurdle in effective treatment of breast carcinoma. The correlation of TRPS1 and BCRP was further confirmed by immunohistochemistry in 180 breast carcinoma samples.…”

Section: Discussionmentioning

confidence: 99%

TRPS1 outperforms GATA3 in pleural effusions with metastatic breast carcinoma versus mesothelioma

Baban

Koepplin

Ahmad

et al. 2023

Diagnostic Cytopathology

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Introduction In evaluating malignant pleural fluid cytology, metastatic adenocarcinomas and mesotheliomas are often differential diagnoses. GATA binding protein 3 (GATA3) has historically been used to confirm metastatic breast carcinomas; however, GATA3 has low specificity if mesothelioma is included in differential diagnoses. Trichorhinophalangeal syndrome type 1 (TRPS1) protein is expressed in all types of breast carcinomas, with reported high specificity and sensitivity. We investigated the performance of TRPS1 immunohistochemistry (IHC) and compared it to GATA3 in pleural fluids diagnosed with metastatic breast carcinoma and mesothelioma. Methods Thirty‐six consecutive ThinPrep pleural fluids and 4 pleural fine needle aspirations (FNAs) with diagnoses of metastatic breast carcinoma (21) and mesothelioma (19) were retrieved, and IHC with TRPS1 and GATA3 was performed on all. Immunoreactivity scores for TRPS1 were calculated by multiplying percentage of immunoreactive cells by staining intensity. Immunoreactivity scores were negative if 0 or 1, low positive if 2, intermediate positive if 3 or 4, or high positive if 6 or 9. Nuclear immunoreactivity of ≥10% with at least moderate intensity was judged GATA3 positive. Results GATA3 showed immunoreactivity in all metastatic breast carcinomas and 84% of mesotheliomas. TRPS1 was immunoreactive in all breast carcinoma cases (18 with a score of 9 and 3 with a score of 6). TRPS1 showed low positivity in 5% of mesothelioma cases with all other cases being negative. Conclusion When cytomorphologic differential diagnoses of mesothelioma exist, TRPS1 is a more specific marker than GATA3 for confirmation of metastatic breast carcinoma in pleural fluid cytology.

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“…According to Hu et al (2020), ABCG2 protein may produce resistance to chemotherapeutic agents. ABCG2 protein is responsible to control the movement of harmful and beneficial substrates such as flavonoids and phytoestrogens across the intestinal cells into the intestinal lumen.…”

Section: Introductionmentioning

confidence: 99%

Mutagenesis Analysis of ABCG2 Gene Promoter of Zebrafish (Danio Rerio)

Yusni

Lim

Chung

2020

TUR

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Breast cancer is the commonest cancer among women worldwide and the probability of a woman dying from breast cancer is high (about 1 in 38 of total human population (2.6%)).The main factor for mortality is due to the resistance of this particular disease to chemotherapeutic agents. One of the most well-known proteins to be found to correlate significantly with breast cancer resistance to chemotherapeutic agent is the ATP-binding cassette super-family G member 2 (ABCG2). Knowledge on ABCG2 gene regulation is still lacking in terms of how the increased cytotoxic levels are closely related to induce a hype in gene transcript levels and ultimately cause of the reduction in chemotherapeutic agents. The approach taken in this study is through mutational analysis of selected transcription factor governing the expression of ABCG2. In order to achieve this, a previously cloned ABCG2 promoter which has been isolated (around 1500 bp in size) from Danio rerio and inserted into pGL3.0 plasmid, was subjected to site-directed mutagenesis. Selected transcription factor which is AP-1 was successfully mutated by deletion of 5'- TGACGCG -3' sequence at position 1113 bp from TSS+1 where it would bind in order to define their role in ABCG2 physiological function. Sequencing result after site-directed mutagenesis shows high similarities about 98% with ABCG2 gene of Danio rerio. Upon validation, it was found that the intended AP-1 binding site has been mutated. In future work, the mutated clone here will be subjected to transfection analysis where dual-luciferase assay will be conducted to verify the loss of activity from the ABCG2 promoter upon mutation of the targeted AP-1 site. Hence, the mutagenesis analysis of ABCG2 promoter are able to provide information on the involvement of AP-1 transcription factor in multidrug resistance mechanism of breast cancer and thus will be a potential target for chemotherapeutic agent.

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TRPS1 Confers Multidrug Resistance of Breast Cancer Cells by Regulating BCRP Expression

Cited by 9 publications

References 43 publications

TRPS1 expression is sensitive and specific for primary extramammary Paget disease

TRPS1 expression is sensitive and specific for primary extramammary Paget disease

TRPS1 outperforms GATA3 in pleural effusions with metastatic breast carcinoma versus mesothelioma

Mutagenesis Analysis of ABCG2 Gene Promoter of Zebrafish (Danio Rerio)

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