Inhibition of the transcription factor AP-1 in cervical cancer

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dc.contributor.advisorLeaner, Virna Den_ZA
dc.contributor.authorMaritz, Michelle Francesen_ZA
dc.date.accessioned2014-07-28T14:55:40Z
dc.date.available2014-07-28T14:55:40Z
dc.date.issued2007en_ZA
dc.descriptionIncludes bibliographical references (leaves 100-110).
dc.description.abstractAP-I is a dimeric transcription factor comprised primarily of Jun and Fos family proteins, that regulates numerous genes involved in cell proliferation, differentiation and oncogenesis. The expression of AP-I is shown to play an important role in many human cancers and plays a key role in the regulation of the E6 and E7 oncoproteins of high-risk Human Papillomaviruses (HPV) that are etiologically associated with cervical cancer. The c-Jun and Jun B components of AP-I were shown to be expressed at higher levels in cervical cancer patients compared to nonnal patient tissue while Jun D levels were largely unchanged. To define the role of AP-I in cervical cancer, the effect of inhibiting AP-I actvity was determined using a dominantnegative deletion mutant T AM67. CaSki cervical cancer cells with a doxycycline inducible T AM67 demonstrated that inhibition of AP-I activity and expression resulted in an altered cell morphology, a significant decrease in cell proliferation and inhibition of colony formation. This was accompanied by a slower progression of T AM67 expressing cells through the cell cycle, with an accompanying increase in G21M phase. An increase in the expression of the cell cycle regulatory protein, p21 CIPI, was observed that appeared independent of p53 expression. siRNA directed at inhibiting individual AP-I components showed that Jun B was an important regulator of CaSki cell proliferation. These results suggest that AP-I is involved in the cell proliferation and tumourigenic phenotype of cervical cancer cells, such as CaSki cells, possibly via a direct repression of cell cycle regulator p21 CIP1en_ZA
dc.identifier.apacitationMaritz, M. F. (2007). <i>Inhibition of the transcription factor AP-1 in cervical cancer</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry. Retrieved from http://hdl.handle.net/11427/3138en_ZA
dc.identifier.chicagocitationMaritz, Michelle Frances. <i>"Inhibition of the transcription factor AP-1 in cervical cancer."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry, 2007. http://hdl.handle.net/11427/3138en_ZA
dc.identifier.citationMaritz, M. 2007. Inhibition of the transcription factor AP-1 in cervical cancer. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Maritz, Michelle Frances AB - AP-I is a dimeric transcription factor comprised primarily of Jun and Fos family proteins, that regulates numerous genes involved in cell proliferation, differentiation and oncogenesis. The expression of AP-I is shown to play an important role in many human cancers and plays a key role in the regulation of the E6 and E7 oncoproteins of high-risk Human Papillomaviruses (HPV) that are etiologically associated with cervical cancer. The c-Jun and Jun B components of AP-I were shown to be expressed at higher levels in cervical cancer patients compared to nonnal patient tissue while Jun D levels were largely unchanged. To define the role of AP-I in cervical cancer, the effect of inhibiting AP-I actvity was determined using a dominantnegative deletion mutant T AM67. CaSki cervical cancer cells with a doxycycline inducible T AM67 demonstrated that inhibition of AP-I activity and expression resulted in an altered cell morphology, a significant decrease in cell proliferation and inhibition of colony formation. This was accompanied by a slower progression of T AM67 expressing cells through the cell cycle, with an accompanying increase in G21M phase. An increase in the expression of the cell cycle regulatory protein, p21 CIPI, was observed that appeared independent of p53 expression. siRNA directed at inhibiting individual AP-I components showed that Jun B was an important regulator of CaSki cell proliferation. These results suggest that AP-I is involved in the cell proliferation and tumourigenic phenotype of cervical cancer cells, such as CaSki cells, possibly via a direct repression of cell cycle regulator p21 CIP1 DA - 2007 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2007 T1 - Inhibition of the transcription factor AP-1 in cervical cancer TI - Inhibition of the transcription factor AP-1 in cervical cancer UR - http://hdl.handle.net/11427/3138 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/3138
dc.identifier.vancouvercitationMaritz MF. Inhibition of the transcription factor AP-1 in cervical cancer. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry, 2007 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/3138en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherMedical Biochemistryen_ZA
dc.titleInhibition of the transcription factor AP-1 in cervical canceren_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMScen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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