Alterations of glutathione and GSTM1 mutations induce tumor metastasis and invasion via EMT pathway in breast cancer patients

Abstract Purpose: Alteration in the Glutathione (GSH) and Glutathione S-Transferase (GST) family lead to various disorders including breast cancer. However, the role of GSH and GSTM1 in the onset of breast cancer is still not fully elucidated. Objective: In the present study we observed considerable deficiency in the levels of glutathione and genetic mutation in the GSTM1 enzyme that influence susceptibility to breast cancer metastasis and invasion via EMT pathway. Methods: GSTM1 genotype was identified by multiplex polymerase chain reaction (PCR), RT-PCR and western blotting in breast cancer tissue samples and ANCT samples. The endogenous glutathione levels were determined by HPLC. The tumor metastasis, invasion and EMT biomarkers were determined by RT-PCR and western blot. The relationship between breast cancer, disease progression and histological status were estimated by one way analysis of variance and descriptive statistic. Data were analyzed using OriginPro 2015 statistics software (OriginLab, Northampton, USA). The correlation among different factors was assessed at 95% confidence intervals (CI) using the Mann-Whitney, Kruskal Wallis, and ANOVA test. P<0.05 was considered significant. Results: In present study genotyping analysis of GST investigated that genetic mutation in GSTM1 was detected in breast cancer tissue samples. Moreover, messenger RNA and protein analysis showed that GSTM1 was significant downregulated in tumor tissues (p=0.005, p=0.02) of breast cancer patients. Furthermore, significant reduction in the level of total glutathione level (GSHt P<0.05) was observed among correlation with patient ages, stages and histological grades, of breast cancer patients. Additionally, the result revealed that downregulation of GSTM1 promotes EMT pathway that leads to enhanced the expression of tumor proliferation, invasion and metastasis in breast cancer tissue samples compared with the ANCT samples (P<0.05). Conclusions The present findings suggest that GSTM1 genotype could be a potential biomarker that regulate EMT pathway associated with breast cancer prognosis.

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SULT1A1 concordance between whole blood and breast cancer tissue

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14090 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14090-14090

Author(s):

J. L. Grabinski ◽

E. Arno ◽

L. S. Smith

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Whole Blood ◽

Breast Cancer Tissue ◽

Clinical Samples ◽

Cancer Tissue ◽

Breast Cancer Patients ◽

Fixed Tissue ◽

Tissue Samples ◽

Formalin Fixed

14090 Background: The human sulfotransferase (SULT1A1) enzyme is involved in the conjugation of tamoxifen. Studies have demonstrated the significance of polymorphisms within the SULT1A1 gene in relation to breast cancer survival and tamoxifen metabolism (Nowell et al, J Natl Cancer Inst 2002). DNA for genotyping in previous studies was obtained from a number of different biological specimens including whole blood or paraffin-embedded formalin-fixed tissue. The purpose of this study was to evaluate the genotypic concordance of SULT1A1 polymorphisms in whole blood and breast cancer tissue. Methods: Breast cancer patients receiving tamoxifen and previously genotyped for the SULT1A1 gene were consented for enrollment. Samples representing each of the three possible genotypes (*1/*1, *1/*2,*2/*2) were selected for the collection of archived tissue. DNA was extracted from whole blood using the QIAamp Blood Midi Kit (Qiagen Inc., Valencia, CA, USA) and from formalin-fixed paraffin-embedded breast cancer tissue using the QIAamp DNA Mini Kit (Qiagen Inc., Valencia, CA, USA) as per protocol. Genotyping of the SULT1A1 gene was conducted using a validated Pyrosequencing assay. Results: Tissue samples representing each of the three different SULT1A1 genotypes were compared to the whole blood genotypes. Each of the clinical samples demonstrated 100% concordance between the two different specimens. Conclusion: Our data provides evidence to support the genotyping of clinical samples for the SULT1A1 gene utilizing either whole blood or tumor tissue from breast cancer patients. No significant financial relationships to disclose.

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Abstract P4-09-10: Prospective Analysis of Fatty Acid Synthase (FASN) in Breast Cancer Tissue of Early-Stage Breast Cancer Patients

10.1158/0008-5472.sabcs12-p4-09-10 ◽

2012 ◽

Author(s):

T Puig ◽

A Blancafort ◽

G Casoliva ◽

G Oliveras ◽

M Casas ◽

...

Keyword(s):

Breast Cancer ◽

Fatty Acid ◽

Cancer Patients ◽

Fatty Acid Synthase ◽

Early Stage ◽

Breast Cancer Tissue ◽

Early Stage Breast Cancer ◽

Cancer Tissue ◽

Prospective Analysis ◽

Breast Cancer Patients

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Evaluation of a quantitative RT-PCR assay to detect HER2 mRNA overexpression for diagnosis and selection of trastuzumab therapy in breast cancer tissue samples

Experimental and Molecular Pathology ◽

10.1016/j.yexmp.2014.09.011 ◽

2014 ◽

Vol 97 (3) ◽

pp. 368-374

Author(s):

Hye-young Wang ◽

Sunghyun Kim ◽

Sangjung Park ◽

Seungil Kim ◽

Dongju Jung ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Tissue ◽

Cancer Tissue ◽

Rt Pcr ◽

Pcr Assay ◽

Tissue Samples ◽

Trastuzumab Therapy ◽

Her2 Mrna ◽

Selection Of

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High Level of Progesteron Receptor Membrane Component 1 (PGRMC 1) in Tissue of Breast Cancer Patients is Associated with Worse Response to Anthracycline-Based Neoadjuvant Therapy

Hormone and Metabolic Research ◽

10.1055/s-0043-113635 ◽

2017 ◽

Vol 49 (08) ◽

pp. 595-603 ◽

Cited By ~ 11

Author(s):

Marina Willibald ◽

Isabel Wurster ◽

Christoph Meisner ◽

Ulrich Vogel ◽

Harald Seeger ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Neoadjuvant Therapy ◽

Cancer Patients ◽

Breast Cancer Tissue ◽

Surrounding Tissue ◽

Cancer Tissue ◽

Breast Cancer Patients ◽

Before And After ◽

Expression Status

AbstractPGRMC1 is known to be highly expressed in breast cancer tissue and is associated with chemoresistance in breast cancer cells. However, its role in breast cancer signaling is not fully understood yet. In the present study, the expression status of PGRMC1 and its phosphorylated version (pPGRMC1) in breast cancer tissue and surrounding stroma before and after neoadjuvant therapy was examined to find a possible association to therapy response. Tissue biopsies of 69 breast cancer patients were analyzed by immunohistochemistry for expression levels of PGRMC1 and pPGRMC1. Expression status of PGRMC1 and pPGRMC1 in tumor tissue was compared with expression status of progesterone receptor (PR), estrogen receptor α (ERα), total estrogen receptor β (ERβ), ERβ1, ERβ2, the proliferation marker Ki-67, and human epidermal growth factor receptor 2 (HER2/neu). Correlations were calculated for expression of PGRMC1 and pPGRMC1 before and after neoadjuvant-therapy. PGRMC1 and pPGRMC1 were highly abundant in every breast cancer tissue sample. Considerably lower signals were detected in surrounding tissue. Further, PGRMC1 and pPGRMC1 abundance was found to correlate with ERβ expression. A lower level of pPGRMC1 could be found in post-therapy surgical specimens compared to specimens before treatment. Interestingly, patients with high PGRMC1 tumor levels showed worse response to anthracycline-based therapy as patients with lower PGRMC1 levels. These new findings demonstrate that PGRMC1 might play an important role in progression and therapy resistance of human breast tumors and could offer an interesting target for anticancer therapy.

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Elevated Luteinizing Hormone in Serum, Breast Cancer Tissue, and Normal Breast Tissue from Breast Cancer Patients

Breast Cancer Research and Treatment ◽

10.1023/a:1020528722842 ◽

2002 ◽

Vol 76 (2) ◽

pp. 125-130 ◽

Cited By ~ 7

Author(s):

Elvio G. Silva ◽

Dinu Mistry ◽

Donghui Li ◽

Henry M. Kuerer ◽

Edward N. Atkinson ◽

...

Keyword(s):

Breast Cancer ◽

Luteinizing Hormone ◽

Cancer Patients ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Normal Breast ◽

Breast Cancer Tissue ◽

Cancer Tissue ◽

Breast Cancer Patients

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Evaluation of HER-2/neu in Serum and Tissue of Primary and Metastatic Breast Cancer Patients using an Automated Enzyme Immunoassay

The International Journal of Biological Markers ◽

10.1177/172460080101600406 ◽

2001 ◽

Vol 16 (4) ◽

pp. 255-261 ◽

Cited By ~ 24

Author(s):

R. Dittadi ◽

M. Zancan ◽

A. Perasole ◽

M. Gion

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Metastatic Breast ◽

Normal Subjects ◽

Continuous Variable ◽

Breast Cancer Tissue ◽

Cancer Tissue ◽

Breast Cancer Patients ◽

Her 2

Serum HER-2/neu concentrations were evaluated in 172 healthy subjects, 176 primary and 55 metastatic breast cancer patients, employing a new automated assay (Bayer Immuno 1™ serum HER-2/neu). Using 13 ng/mL as the cutoff, abnormal HER-2/neu serum levels were found in 8% (14/176) of primary and 50.9% (28/55) of metastatic breast cancer patients. Both in primary and metastatic breast cancer a significant relationship was found with the stage of the disease when serum HER-2/neu was considered as a categorized variable (p=0.0003 and p=0.02, respectively), but not when it was taken as a continuous variable (p=0.247 and p=0.146, respectively). Moreover, we evaluated the correlation between Immuno 1™ HER-2/neu and Oncogene Research Products ELISA assay in 53 normal subjects, 46 primary and 34 metastatic breast cancer patients. The correlation was relatively good (p<0.0001), although substantial differences could be found in single cases. The Immuno 1™ assay was also evaluated for the first time in breast cancer tissue. The method, which showed good performance both in terms of imprecision and linearity, was used to measure HER-2/neu protein in 140 cytosol samples from primary breast cancer tissue and in homogenates from 40 matched cases. The correlation between the two matrixes was very close (p<0.0001). By contrast, no correlation was found between serum and matched cytosol (p=0.101) or ho-mogenate samples (p=0.511).

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