Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
The effect of seminal fluid on TBx2 and TBX3 expression and activity in cervical cancer cells
Cervical cancer is one of the most common female cancers in Africa, both in terms of incidence and mortality, and is disproportionately prevalent in developing nations due to a lack of adequate access to healthcare. While new vaccine technologies are rapidly reducing the incidence of Human Papilloma...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Division of Medical Biochemistry and Structural Biology
2017
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613865753182208 |
|---|---|
| access_status_str | Open Access |
| author | Cooper, George William |
| author2 | Katz, Arieh |
| author_browse | Cooper, George William Katz, Arieh |
| author_facet | Katz, Arieh Cooper, George William |
| author_sort | Cooper, George William |
| collection | Thesis |
| description | Cervical cancer is one of the most common female cancers in Africa, both in terms of incidence and mortality, and is disproportionately prevalent in developing nations due to a lack of adequate access to healthcare. While new vaccine technologies are rapidly reducing the incidence of Human Papilloma Virus (HPV) infection, the primary causative agent of cervical cancer, new cases continue to accumulate in the developing world. Beyond the role of HPV in the early stages of cancer development, the molecular aetiology of this disease is poorly understood. Frequent exposure to seminal fluid (SF), the liquid component of semen, has been proposed as a potential driver of oncogenesis in cervical cancers and has been shown to exacerbate some aspects of cervical cancers. While some of the cellular signaling pathways responsible for these phenomena have been identified, much remains to be elucidated. We hypothesized that TBX2 and TBX3, two highly homologous transcription factors frequently implicated in other cancers, may be responsible for mediating some of the effects of SF on cervical cancer cells. We established that TBX3 protein is significantly overexpressed in both primary cervical adenocarcinomas and squamous cell carcinomas compared to normal tissue. SF was shown to increase expression of both TBX2 and TBX3 mRNA in HeLa and CaSki, but not C-33 A, cervical cancer cell lines. Furthermore, SF upregulated TBX3 protein expression in both of these cell lines. In contrast, TBX2 protein was undetectable in these cell lines. In addition, our results showed that SF treatment of HeLa cells increases the expression of the known TBX3 target gene, p21CIP1/WAF1 (p21), while having no effect on PTEN expression. Transient knockdown of TBX3 resulted in decreased p21 expression in SF-treated cells suggesting that SF upregulation of p21 is dependent on TBX3. This is the first study to investigate TBX3 protein expression in primary cervical tissues and SF regulation of TBX3. However, further research is required in order to elucidate the role of SF-induced TBX3 in cervical cancer development. The identification of the role of TBX3 in cervical cancer development could aid in the development of more effective treatments for cervical cancers and could potentially impact sexual health policy recommendations for women with cervical cancer. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/24886 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:42:56.733Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| publisher | Division of Medical Biochemistry and Structural Biology |
| publisherStr | Division of Medical Biochemistry and Structural Biology |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/24886 The effect of seminal fluid on TBx2 and TBX3 expression and activity in cervical cancer cells Cooper, George William Katz, Arieh Prince, Sharon Medical Biochemistry Cervical cancer is one of the most common female cancers in Africa, both in terms of incidence and mortality, and is disproportionately prevalent in developing nations due to a lack of adequate access to healthcare. While new vaccine technologies are rapidly reducing the incidence of Human Papilloma Virus (HPV) infection, the primary causative agent of cervical cancer, new cases continue to accumulate in the developing world. Beyond the role of HPV in the early stages of cancer development, the molecular aetiology of this disease is poorly understood. Frequent exposure to seminal fluid (SF), the liquid component of semen, has been proposed as a potential driver of oncogenesis in cervical cancers and has been shown to exacerbate some aspects of cervical cancers. While some of the cellular signaling pathways responsible for these phenomena have been identified, much remains to be elucidated. We hypothesized that TBX2 and TBX3, two highly homologous transcription factors frequently implicated in other cancers, may be responsible for mediating some of the effects of SF on cervical cancer cells. We established that TBX3 protein is significantly overexpressed in both primary cervical adenocarcinomas and squamous cell carcinomas compared to normal tissue. SF was shown to increase expression of both TBX2 and TBX3 mRNA in HeLa and CaSki, but not C-33 A, cervical cancer cell lines. Furthermore, SF upregulated TBX3 protein expression in both of these cell lines. In contrast, TBX2 protein was undetectable in these cell lines. In addition, our results showed that SF treatment of HeLa cells increases the expression of the known TBX3 target gene, p21CIP1/WAF1 (p21), while having no effect on PTEN expression. Transient knockdown of TBX3 resulted in decreased p21 expression in SF-treated cells suggesting that SF upregulation of p21 is dependent on TBX3. This is the first study to investigate TBX3 protein expression in primary cervical tissues and SF regulation of TBX3. However, further research is required in order to elucidate the role of SF-induced TBX3 in cervical cancer development. The identification of the role of TBX3 in cervical cancer development could aid in the development of more effective treatments for cervical cancers and could potentially impact sexual health policy recommendations for women with cervical cancer. 2017-08-17T14:12:16Z 2017-08-17T14:12:16Z 2017 Master Thesis Masters MSc (Med) http://hdl.handle.net/11427/24886 eng application/pdf Division of Medical Biochemistry and Structural Biology Faculty of Health Sciences University of Cape Town |
| spellingShingle | Medical Biochemistry Cooper, George William The effect of seminal fluid on TBx2 and TBX3 expression and activity in cervical cancer cells |
| thesis_degree_str | Master's |
| title | The effect of seminal fluid on TBx2 and TBX3 expression and activity in cervical cancer cells |
| title_full | The effect of seminal fluid on TBx2 and TBX3 expression and activity in cervical cancer cells |
| title_fullStr | The effect of seminal fluid on TBx2 and TBX3 expression and activity in cervical cancer cells |
| title_full_unstemmed | The effect of seminal fluid on TBx2 and TBX3 expression and activity in cervical cancer cells |
| title_short | The effect of seminal fluid on TBx2 and TBX3 expression and activity in cervical cancer cells |
| title_sort | effect of seminal fluid on tbx2 and tbx3 expression and activity in cervical cancer cells |
| topic | Medical Biochemistry |
| url | http://hdl.handle.net/11427/24886 |
| work_keys_str_mv | AT coopergeorgewilliam theeffectofseminalfluidontbx2andtbx3expressionandactivityincervicalcancercells AT coopergeorgewilliam effectofseminalfluidontbx2andtbx3expressionandactivityincervicalcancercells |