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

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).

2020 ◽  
Author(s):  
Shahan Mamoor

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).


2020 ◽  
Author(s):  
Shahan Mamoor

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).


2020 ◽  
Author(s):  
Shahan Mamoor

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).


2020 ◽  
Author(s):  
Shahan Mamoor

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).


2020 ◽  
Author(s):  
Shahan Mamoor

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).


2020 ◽  
Author(s):  
Shahan Mamoor

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).


2020 ◽  
Author(s):  
Shahan Mamoor

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.


2020 ◽  
Author(s):  
Shahan Mamoor

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).


2020 ◽  
Author(s):  
Shahan Mamoor

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.


2020 ◽  
Author(s):  
Shahan Mamoor

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.


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