Increased Expression of BRCA2 and RAD51 in Lymph Node Metastases of Canine Mammary Adenocarcinomas

2009 ◽  
Vol 46 (3) ◽  
pp. 416-422 ◽  
Author(s):  
R. Klopfleisch ◽  
A. D. Gruber

The BRCA/RAD51 complex of tumor suppressor genes plays a major role in the DNA damage response. In this explorative study, BRCA1, BRCA2, and RAD51 mRNA expression was quantified in highly defined laser microdissected tissue samples of simple adenomas, adenocarcinomas of the mammary gland, and their lymph node metastases by real-time quantitative reverse transcription polymerase chain reaction. Expression levels in the tumors were normalized to the geometric mean of 3 housekeeping genes and quantified relative to normal mammary epithelium of the same dog. In adenomas, mRNA expression was reduced for BRCA1 (6/10 dogs, 60%), BRCA2 (4/10 dogs, 40%), and RAD51 (4/10, 40%). In adenocarcinomas BRCA1 expression varied with increased expression in 3 of 10 (30%) dogs and no differences in 7 of 10 (70%) dogs when compared with normal mammary gland. BRCA2 and RAD51 were overexpressed in 5 of 10 (50%) and 6 of 10 (60%) of adenocarcinomas, respectively. An overexpression of RAD51 and BRCA2 was found in 8 of 10 (80%) and 5 of 10 (50%) of the lymph node metastases, respectively. Direct comparison of primary tumors and metastases revealed increased mRNA expression of BRCA1 (2/10 dogs, 20%), BRCA2 (2/10 dogs, 20%), and RAD51 (3/10 dogs, 30%) in lymph node metastases. Taken together, the results suggest that RAD51 is upregulated in the majority of lymph node metastases of canine mammary tumors. Further experimental studies are needed to clarify whether these changes in gene expression are a direct carcinogenetic stimulus or a protective response due to genetic instability during tumor progression.

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Marie-Charlotte von Deetzen ◽  
Bernd T. Schmeck ◽  
Achim D. Gruber ◽  
Robert Klopfleisch

MicroRNA has been suspected to be generally involved in carcinogenesis since their first description. A first study supported this assumption for canine mammary tumors when miRNA expression was compared to normal gland. The present study extends these results by comparing the expression of 16 microRNA (miRNA) and 4 small nucleolar RNA (snoRNA) in tumors of different malignancy, for example, adenomas, nonmetastasizing and metastasizing carcinomas as well as lymph node metastases, with each other and with normal mammary gland. All neoplastic tissues differed in their miR-210 expression levels from normal gland. While metastatic cells differed in their expression of mir-29b, miR-101, mir-125a, miR-143, and miR-145 from primary tumors, the comparison of miRNA expression in primary tumors of different malignancy failed to reveal significant differences except for a significant downregulation of mir-125a in metastasizing carcinomas when compared to adenomas.


2021 ◽  
Vol 81 ◽  
pp. 105720
Author(s):  
Youssef Oukessou ◽  
Yassir Hammouda ◽  
Khadija El Bouhmadi ◽  
Redallah Larbi Abada ◽  
Mohamed Roubal ◽  
...  

2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that collagen type XVI alpha 1 chain, COL16A1, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. COL16A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL16A1 in primary tumors of the breast was correlated with patient overall survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL16A1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that collagen type VI alpha 1 chain, COL6A1, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. COL6A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL6A1 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL6A1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that teashirt zinc finger homeobox 3, TSHZ3, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TSHZ3 was also differentially expressed in brain metastatic tissues. TSHZ3 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TSHZ3 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TSHZ3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that transmembrane protein 98, TMEM98, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TMEM98 was also differentially expressed in brain metastatic tissues. TMEM98 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TMEM98 in primary tumors of the breast was correlated with patient overall survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TMEM98 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that cluster of differentiation 69, CD69, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that CD69 was also differentially expressed in brain metastatic tissues. CD69 mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of CD69 in primary tumors of the breast was correlated with patient overall survival, more significantly in lymph node negative patients than in lymph node positive patients. Modulation of CD69 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that diaphanous homolog 2, encoded by DIAPH2, was among the genes whose expression was most different in the brain and lymph node metastases of patients with metastatic breast cancer. DIAPH2 mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of DIAPH2 in primary tumors was significantly correlated with patient recurrence-free survival in patients with breast cancer. Modulation of DIAPH2 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain while evading immune clearance in the lymph nodes in humans with metastatic breast cancer. These data are one piece of evidence suggesting a common ancestor or tumor clone for brain and lymph node metastases that originate from the primary tumor, alluding to patterns in developmental origin and migratory pathways through the lymph node in human brain metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that EvC ciliary complex subunit 1, EVC, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. EVC mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of EVC in primary tumors of the breast was correlated with patient overall survival, in lymph node positive patients but not in lymph node negative patients. Modulation of EVC expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that natural cytotoxicity triggering receptor 1, NCR1, also known as CD335 or NKp46,was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. NCR1 mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of NCR1 in primary tumors of the breast was correlated with patient recurrence-free survival, more significantly in lymph node negative patients than in lymph node positive patients. Modulation of NCR1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


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