scholarly journals Trastuzumab administration in patients with breast cancer is associated with increased primary tumor expression of SH3BP2.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Binding Partner ◽  
Syk Kinase ◽  
Src Homology ◽  
Epidermal Growth ◽  
Tumor Expression

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the cell signaling intermediate and Src homology domain binding protein SH3BP2, also known as 3BP2, was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab. 3BP2 is a binding partner of the Syk kinase (5, 6); we recently described differential and increased expression of Syk in the tumors of breast cancer patients treated with trastuzumab (7); thus, trastuzumab may likely be associated with activation of Syk kinase signal transduction in primary tumors of patients with breast cancer.

scholarly journals Trastuzumab administration in patients with breast cancer is associated with increased primary tumor expression of STAT3.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Constitutive Expression ◽  
Growth Factor Receptor ◽  
Signal Transduction Pathway ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Epidermal Growth ◽  
Tumor Expression

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the cell signaling intermediate signal transducer and activator of transcription STAT3 was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab. STAT3 was expressed at significantly higher levels in the tumors of patients treated with trastuzumab, indicating that trastuzumab is potentially associated with activation of a signal transduction pathway important for survival of breast cancer cells, and demonstrating that a molecule described as an oncogene (5) with constitutive expression in all cell lines transformed by the Src proto-oncogene (6) is present at significantly higher quantities in the tumors of breast cancer patients treated with trastuzumab.

scholarly journals Frizzled class receptor 7 is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Embryonic Stem ◽  
Growth Factor Receptor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Complete Understanding ◽  
Primary Tumors ◽  
Epidermal Growth

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the Wnt pathway receptor frizzled-7, FZD7, was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at significantly higher levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with increased expression of a signal transduction receptor that can support proliferation of triple negative breast cancer cells (5) and is required for the maintenance of pluripotency of human embryonic stem cells (6).

scholarly journals Trastuzumab administration in patients with breast cancer is associated with increased primary tumor expression of IL-1β.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Gene Encoding ◽  
Primary Tumors ◽  
Cancer Models ◽  
Epidermal Growth ◽  
Tumor Expression

A complete understanding of how tumor signal transduction in human breast cancer is modulated by trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) (1, 2), is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the gene encoding interleukin-1β (5), IL1β, was among those most differentially expressed in the primary tumors of patients treated with trastuzumab. IL1β was expressed at significantly higher levels in the tumors of patients treated with trastuzumab, indicating that a cytokine associated with metastasis to the bones in cancer models (6-9) and correlated with relapse of disease to the bones in human breast cancer (8) is produced at significantly higher quantities in the tumors of breast cancer patients treated with trastuzumab.

scholarly journals The placental growth factor (PGF) is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Placental Growth Factor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Epidermal Growth ◽  
The Brain

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the placental growth factor, encoded by PGF was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at lower levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with increased expression of a growth factor that is chemotactic, angiogenic (5) and important for growth of blood vessels in the brain (6).

scholarly journals Six homeobox 6 (SIX6) is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Visual Processing ◽  
Growth Factor Receptor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Optic Stalk ◽  
The Central Nervous System ◽  
Epidermal Growth

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the six homeobox 6, SIX6, was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at higher levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with activation of a gene important for maintenance of multipotent retinal progenitors and expressed in regions of the central nervous system involved in visual processing including the optic stalk and retina (5-8).

scholarly journals Differential expression of PTK7 in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Differential Expression ◽  
Protein Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Transcriptional Responses ◽  
Primary Tumors ◽  
Epidermal Growth ◽  
Protein Tyrosine Kinase 7

The mechanism of action underlying trastuzumab (Herceptin) function is thought to be binding of the Fab region of trastuzumab to the extracellular domain of the human epidermal growth factor receptor (HER2) (1). The transcriptional responses that follow signals transduced after trastuzumab binding of HER2 are less well understood. We mined published microarray and multiplexed gene expression data (2-4) to understand in an unbiased fashion genes most differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab. We observed significantly increased and differential expression of the protein tyrosine kinase 7, PTK7 (5-7).

scholarly journals A second erb-B receptor tyrosine kinase, ERBB4, is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Trastuzumab Treatment ◽  
Erbb2 Gene ◽  
Epidermal Growth

HER2, the human epidermal growth factor receptor 2, is encoded by the ERBB2 gene (1). Trastuzumab, a monoclonal antibody that targets HER2, is utilized for the treatment of breast cancer (2). We recently reported that trastuzumab treatment paradoxically increases HER2 expression in the primary tumors of patients with breast cancer (3). We report here, using analysis of published microarray data (4, 5), that a second erb-B receptor tyrosine kinase, ERRB4, is also differentially expressed in the tumors of patients with breast cancer treated with trastuzumab. Trastuzumab treatment appears to be associated with the up-regulation of two members of the erb-B receptor tyrosine kinase family in human breast cancer.

scholarly journals ITGβ1 (CD29) is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Messenger Rna ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
The United States ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Tumor Expression

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified the cell adhesion molecule integrin β1 (5-9) as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed significantly higher levels of ITGβ1 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of ITGβ1 in primary tumors of the breast, suggesting that increased primary tumor expression of ITGβ1 in the primary tumors of patients with breast cancer, a molecule whose increased expression in human breast cancer is correlated with overall survival, metastasis and significantly decreased time from diagnosis to death (10, 11), is a direct transcriptional result of treatment with trastuzumab.

scholarly journals BIRC3 is a differentially expressed gene in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differentially Expressed Gene ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
The United States ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Unbiased Manner ◽  
Epidermal Growth

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We found that BIRC3 was among the the genes most differentially expressed in the primary tumors of patients treated with trastuzumab. BIRC3, a molecule with the capacity to promote the survival of cancer cells (5), was expressed at significantly higher levels in the primary tumors of patients treated with trastuzumab as compared to that of patients not treated with trastuzumab.

scholarly journals TNFSF8 (CD153 / CD30L) is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Messenger Rna ◽  
Growth Factor Receptor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Complete Understanding ◽  
Primary Tumors ◽  
Trastuzumab Treatment ◽  
Epidermal Growth

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that TNFSF8, also known as CD153 and CD30 ligand (CD30L) was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab. TNFSF8 messenger RNA expression was significantly enhanced in the primary tumors of patients treated with trastuzumab. Thus, trastuzumab treatment in patients with breast cancer is associated with increased expression, in primary tumors of the breast, of a marker with broad expression in multiple human cancers of the hematopoietic system (5, 6), and with the capacity to regulate immunoglobulin class switching (7).

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