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

2020 ◽  
Author(s):  
Shahan Mamoor

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).

2020 ◽  
Author(s):  
Shahan Mamoor

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).


2020 ◽  
Author(s):  
Shahan Mamoor

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.


2020 ◽  
Author(s):  
Shahan Mamoor

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 through trastuzumab binding to 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 Wilms’ tumor susceptibility gene, WT1 in the tumors of breast cancer patients treated with trastuzumab.


2020 ◽  
Author(s):  
Shahan Mamoor

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.


2020 ◽  
Author(s):  
Shahan Mamoor

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.


2020 ◽  
Author(s):  
Shahan Mamoor

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 and public microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified significant differential expression of the gene encoding the Wnt pathway molecule dishevelled-3, DVL3 (5-7), in the primary tumors of breast cancer patients treated with trastuzumab. DVL3 expression in primary tumors of the breast in patients treated with trastuzumab was significantly higher than in patients not 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 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

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 deleted in colorectal cancer locus DCC (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 DCC messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of DCC in primary tumors of the breast, demonstrating that a gene encoding for a netrin receptor, cellular machinery utilized for axon guidance in the central nervous system (5-9), is transcriptionally induced in primary tumors of the breast following treatment 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 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).


Oncology ◽  
1996 ◽  
Vol 53 (6) ◽  
pp. 441-447 ◽  
Author(s):  
Matthias W. Beckmann ◽  
Dieter Niederacher ◽  
Gero Massenkeil ◽  
Boris Tutschek ◽  
Andreas Beckmann ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document