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

Breast Cancer Patients ◽

Primary Tumors ◽

Trastuzumab Treatment ◽

Erbb2 Gene ◽

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.

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).

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 ◽

Transcriptional Responses ◽

Primary Tumors ◽

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 observed significantly increased and differential expression of the neurotrophic receptor tyrosine kinase receptor 2, NTRK2 (4, 5).

Bcl-XL (BCL2L1) is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

10.31219/osf.io/jxvdy ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Messenger Rna ◽

Growth Factor Receptor ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Trastuzumab Treatment ◽

Apoptotic Protein ◽

Cellular Machinery ◽

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 anti-apoptotic protein Bcl-XL, also known as BCL2L1 was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab. BCL2L1 messenger RNA expression was markedly 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 cellular machinery that prevents cell death (5-9).

YES1 tyrosine kinase is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

10.31219/osf.io/dt7bs ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Tyrosine Kinase ◽

Growth Factor Receptor ◽

Expression Data ◽

Breast Cancer Patients ◽

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 tyrosine kinase YES1 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 proto-oncogenic tyrosine kinase (5) that can support growth and metastasis of lung cancer cells in vitro and in vivo (6).

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).

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

10.31219/osf.io/sj2fb ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Tyrosine Kinase ◽

Cancer Patients ◽

Messenger Rna ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

The United States ◽

Breast Cancer Patients ◽

Primary Tumors

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 megakaryocyte-associated tyrosine kinase MATK (5, 6) 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 MATK messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of MATK in primary tumors of the breast, demonstrating that a platelet-expressed tyrosine kinase (5, 6) that interacts with the receptor for the stem cell factor (7) is likely transcriptionally induced in primary tumors of the breast by trastuzumab.

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).

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

10.31219/osf.io/9evh4 ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Differentially Expressed Gene ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

The United States ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Unbiased Manner ◽

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.

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.