Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
Correlating the expression levels of COBRA1 (co-factor of BRCA1) with hepatocellular carcinoma development in Egyptian patients
COBRA1 is a co-factor of BRCA1 that was identified to be the β-subunit of the NELF complex (Negative elongation factor) which stalls RNA polymerase II and prevents elongation of the message. The reported levels of expression of COBRA1 (NELF-B) in different types of cancers varied; COBRA1 is d...
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis |
| Published: |
AUC Knowledge Fountain
2013
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613419158372352 |
|---|---|
| access_status_str | Open Access |
| author | Kamel, Sarah |
| author_browse | Kamel, Sarah |
| author_facet | Kamel, Sarah |
| author_sort | Kamel, Sarah |
| collection | Thesis |
| dc_rights_str_mv | The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. The author has granted the American University in Cairo or its agents a non-exclusive license to archive this thesis, dissertation, paper, or record of study, and to make it accessible, in whole or in part, in all forms of media, now or hereafter known. |
| description | COBRA1 is a co-factor of BRCA1 that was identified to be the β-subunit of the NELF complex (Negative elongation factor) which stalls RNA polymerase II and prevents elongation of the message. The reported levels of expression of COBRA1 (NELF-B) in different types of cancers varied; COBRA1 is down-regulated in breast cancer, whereas in the upper gastrointestinal carcinomas it is up-regulated. The exact role of COBRA1 being a tumor suppressor gene or an oncogene remains unclear. To date, the levels of expression of COBRA1 in Hepatocellular Carcinomas (HCCs) are not yet tested. In an attempt to understand part of the complicated molecular events involved in the development of HCC, we collected 16 primary HCC tissues and their corresponding non-neoplastic specimens from patients undergoing either liver resection or liver transplantation. Samples were divided into two categories; those which undergone treatment prior to surgical procedure, TACE (Transarterial Chemoembolization) or radiofrequency ablation, and others that were not treated. All samples were examined at the RNA and protein levels using RT-PCR and western blotting respectively. All the results were quantified and normalized to the endogenous housekeeping gene using ImageJ software. The levels of expression were calculated relative to the expression of the corresponding non-neoplastic tissue. COBRA1 expression was tested and correlated to other molecules that were reported to be deregulated in HCC and were thought to be linked to COBRA1. These molecules were NANOG which is a marker for cell stemness; β-CATENIN a key player in the Wnt signaling pathway. We found that the transcript levels of COBRA1 were elevated in the entire cohort of the untreated cancer specimens when compared to the corresponding non-neoplastic tissues. The protein level of COBRA1 on the other hand, was elevated in only 6 untreated HCC specimens. The protein expressed by the NANOG and β-CATENIN was found to be up-regulated simultaneously with the COBRA1 in four samples. Unlike the untreated samples, treated cancer specimens displayed a decreased expression of COBRA1, NANOG and β-CATENIN. Our results propose COBRA1 as a novel oncogene in HCCs that may be used as a prognostic marker. |
| format | Thesis |
| id | oai:fount.aucegypt.edu:etds-2591 |
| institution | American University in Cairo (Egypt) |
| last_indexed | 2026-06-10T12:35:50.652Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from AUC Knowledge Fountain — bepress |
| publishDate | 2013 |
| publishDateRange | 2013 |
| publishDateSort | 2013 |
| publisher | AUC Knowledge Fountain |
| publisherStr | AUC Knowledge Fountain |
| record_format | dspace |
| source_str | AUC Knowledge Fountain — bepress |
| spelling | oai:fount.aucegypt.edu:etds-2591 Correlating the expression levels of COBRA1 (co-factor of BRCA1) with hepatocellular carcinoma development in Egyptian patients Kamel, Sarah COBRA1 is a co-factor of BRCA1 that was identified to be the β-subunit of the NELF complex (Negative elongation factor) which stalls RNA polymerase II and prevents elongation of the message. The reported levels of expression of COBRA1 (NELF-B) in different types of cancers varied; COBRA1 is down-regulated in breast cancer, whereas in the upper gastrointestinal carcinomas it is up-regulated. The exact role of COBRA1 being a tumor suppressor gene or an oncogene remains unclear. To date, the levels of expression of COBRA1 in Hepatocellular Carcinomas (HCCs) are not yet tested. In an attempt to understand part of the complicated molecular events involved in the development of HCC, we collected 16 primary HCC tissues and their corresponding non-neoplastic specimens from patients undergoing either liver resection or liver transplantation. Samples were divided into two categories; those which undergone treatment prior to surgical procedure, TACE (Transarterial Chemoembolization) or radiofrequency ablation, and others that were not treated. All samples were examined at the RNA and protein levels using RT-PCR and western blotting respectively. All the results were quantified and normalized to the endogenous housekeeping gene using ImageJ software. The levels of expression were calculated relative to the expression of the corresponding non-neoplastic tissue. COBRA1 expression was tested and correlated to other molecules that were reported to be deregulated in HCC and were thought to be linked to COBRA1. These molecules were NANOG which is a marker for cell stemness; β-CATENIN a key player in the Wnt signaling pathway. We found that the transcript levels of COBRA1 were elevated in the entire cohort of the untreated cancer specimens when compared to the corresponding non-neoplastic tissues. The protein level of COBRA1 on the other hand, was elevated in only 6 untreated HCC specimens. The protein expressed by the NANOG and β-CATENIN was found to be up-regulated simultaneously with the COBRA1 in four samples. Unlike the untreated samples, treated cancer specimens displayed a decreased expression of COBRA1, NANOG and β-CATENIN. Our results propose COBRA1 as a novel oncogene in HCCs that may be used as a prognostic marker. 2013-01-10T08:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/1555 https://fount.aucegypt.edu/context/etds/article/2591/viewcontent/auto_convert.pdf The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. The author has granted the American University in Cairo or its agents a non-exclusive license to archive this thesis, dissertation, paper, or record of study, and to make it accessible, in whole or in part, in all forms of media, now or hereafter known. Theses and Dissertations AUC Knowledge Fountain Biotechnology Liver--Cancer |
| spellingShingle | Biotechnology Liver--Cancer Kamel, Sarah Correlating the expression levels of COBRA1 (co-factor of BRCA1) with hepatocellular carcinoma development in Egyptian patients |
| title | Correlating the expression levels of COBRA1 (co-factor of BRCA1) with hepatocellular carcinoma development in Egyptian patients |
| title_full | Correlating the expression levels of COBRA1 (co-factor of BRCA1) with hepatocellular carcinoma development in Egyptian patients |
| title_fullStr | Correlating the expression levels of COBRA1 (co-factor of BRCA1) with hepatocellular carcinoma development in Egyptian patients |
| title_full_unstemmed | Correlating the expression levels of COBRA1 (co-factor of BRCA1) with hepatocellular carcinoma development in Egyptian patients |
| title_short | Correlating the expression levels of COBRA1 (co-factor of BRCA1) with hepatocellular carcinoma development in Egyptian patients |
| title_sort | correlating the expression levels of cobra1 co factor of brca1 with hepatocellular carcinoma development in egyptian patients |
| topic | Biotechnology Liver--Cancer |
| url | https://fount.aucegypt.edu/etds/1555 https://fount.aucegypt.edu/context/etds/article/2591/viewcontent/auto_convert.pdf |
| work_keys_str_mv | AT kamelsarah correlatingtheexpressionlevelsofcobra1cofactorofbrca1withhepatocellularcarcinomadevelopmentinegyptianpatients |