Differential expression of Notch4 in the primary tumors of breast cancer patients treated with trastuzumab.

Primary Tumors ◽

Over Expression ◽

The mechanism of action underlying trastuzumab (Herceptin) function is ascribed to 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, 3) to understand in an unbiased fashion genes most differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab. We found significant differential and over-expression of Notch4 (4, 5), described as a mammary proto-oncogene (4), in the primary tumors of breast cancer patients treated with trastuzumab.

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

10.31219/osf.io/xf6hc ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Differential Expression ◽

Protein Tyrosine Kinase ◽

Growth Factor Receptor ◽

Breast Cancer Patients ◽

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).

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

10.31219/osf.io/pdtz5 ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Growth Factor ◽

Growth Factor Receptor ◽

Placental Growth Factor ◽

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).

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

10.31219/osf.io/t58ze ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Visual Processing ◽

Growth Factor Receptor ◽

Expression Data ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Optic Stalk ◽

The Central Nervous System ◽

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).

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

10.31219/osf.io/m2dgf ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Messenger Rna ◽

Growth Factor Receptor ◽

Expression Data ◽

Breast Cancer Patients ◽

Complete Understanding ◽

Primary Tumors ◽

Trastuzumab Treatment ◽

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).

TNFAIP1 is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

10.31219/osf.io/tvy46 ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Growth Factor Receptor ◽

Expression Data ◽

Breast Cancer Patients ◽

Necrosis Factor Alpha ◽

Primary Tumors ◽

Epidermal Growth ◽

Factor Alpha ◽

Necrosis Factor

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 tumor necrosis factor alpha-induced protein 1, TNFAIP1, 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 decreased expression of a gene (5) that can induce apoptosis of cancer cells (6).

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

10.31219/osf.io/28q65 ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

The United States ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Transcriptional Changes ◽

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.

Trastuzumab treatment in patients with breast cancer is associated with differential expression of the neurotrophic receptor tyrosine kinase receptor NTRK2.

10.31219/osf.io/4hp6u ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Tyrosine Kinase ◽

Differential Expression ◽

Receptor Tyrosine Kinase ◽

Growth Factor Receptor ◽

Tyrosine Kinase Receptor ◽

Breast Cancer Patients ◽

Primary Tumors ◽

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

10.31219/osf.io/aq5uv ◽

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.

SYK, CSK and FYN are differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

10.31219/osf.io/d7zw9 ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tyrosine Kinases ◽

Growth Factor Receptor ◽

Protein Tyrosine Kinases ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Protein Tyrosine

The mechanism of action underlying trastuzumab (Herceptin) function is ascribed to 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. Protein tyrosine kinases are one major class of cellular components utilized in the transduction of signals from the cell surface to the nucleus. We mined published microarray and multiplexed gene expression data (2-5) 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 multiple protein tyrosine kinases in the primary tumors of patients with breast cancer, including SYK, CSK and FYN. These data document previously undescribed up-regulation of protein tyrosine kinases following treatment with trastuzumab in patients with breast cancer.

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

10.31219/osf.io/hqgax ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Signal Transduction ◽

Embryonic Stem ◽

Growth Factor Receptor ◽

Expression Data ◽

Breast Cancer Patients ◽

Complete Understanding ◽

Primary Tumors ◽

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).