scholarly journals Trastuzumab supports transcription of genes associated with proliferation in human breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Human Breast Cancer ◽  
Growth Factor Receptor ◽  
Nuclear Antigen ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Primary Tumors ◽  
Transcriptional Changes ◽  
Epidermal Growth

The mechanism of action associated with trastuzumab function in breast cancer is thought to involve binding of the Fab domain of trastuzumab to the extracellular portion of the human epidermal growth factor receptor 2 (HER2) (1), but the transcriptional changes induced by signals transduced by this binding event are less described. We mined published and public microarray data (2-5) to understand in an unbiased fashion and at the systems level genes most differentially expressed in the tumors of breast cancer patients treated with trastuzumab. We discovered significant perturbation of genes associated with cell proliferation - most significantly but not restricted to the proliferating cell nuclear antigen, PCNA. Significant transcriptional induction of PCNA in the primary tumors of patients with breast cancer following administration of trastuzumab alludes to a seemingly paradoxical role for trastuzumab in support of tumor cell proliferation in human breast cancer.

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 Disks large homolog 3 (DLG3) is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

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

Trastuzumab (Herceptin), a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1), is 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 fashion the most significant transcriptional changes associated with treatment with trastuzumab in patients with breast cancer. We identified disks large homolog 3 (DLG3) 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 higher levels of DLG3 than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to drive differential expression of DLG3 in primary tumors of the breast, demonstrating that a gene whose expression is associated with decreased survival in patients with breast cancer (5) is transcriptionally induced in primary tumors of the breast as a result of treatment with trastuzumab.

scholarly journals Platelet-derived growth factors α and β are differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Growth Factors ◽  
Growth Factor Receptor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
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 platelet-derived growth factors α and β , PDGF-α and PDGF-β, are 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 growth factors important for development of the neural crest and neural tube (5,6).

scholarly journals GAS7 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 Receptor ◽  
Differentially Expressed ◽  
Specific Gene ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
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 growth arrest-specific gene 7, GAS7, 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 gene (5) that can induce neurite outgrowth and support survival of acute lymphoblastic leukemias (6).

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 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).

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