Defeciancy Of Puma And Noxa For Melanomagenesis In A Mouse Model Of Melanoma

dc.contributor.authorPhang, Su Ling
dc.date.accessioned2019-09-04T07:54:09Z
dc.date.available2019-09-04T07:54:09Z
dc.date.issued2017-07
dc.description.abstractIt is commonly believed without sufficient evidence that the impairment of the ability to undergo apoptosis (a mode of programmed cell death) in response to conventional treatment such as cytotoxic drugs, gained melanoma its notorious resistance to therapy. Studies to determine the contribution of the intrinsic apoptosis pathway for melanomagenesis are often deterred by utilisation of in vitro cell culture models and xenograft models. An established mouse model of melanoma, the Cdkn2a -/-, Tyr-HRASG12V, was utilised in this study to obviate limitations posted by the usage of in vitro and xenograft models. The Cdkn2a -/-, Tyr-HRASG12V was crossed with either a Puma -/- or Noxa -/- line yielding in Cdkn2a-/-, Tyr-HRASG12V, Noxa -/- or Cdkn2a -/-, Tyr-HRASG12V, Puma -/- strains respectively. Generation of these strains enabled us to investigate the significance of the intrinsic apoptosis pathway for melanomagenesis. The BH3-only proteins Puma and Noxa were chosen as relevant proteins to be exploited in the apoptosis pathway as there are evidence from other studies reporting on their involvement in melanoma biology and treatment response. Here, we report that tumours from all three cohorts were stained for gold standard markers HMB45, S100 and MelanA and were confirmed as melanoma. Loss of Puma only marginally accelerated melanomagenesis compared to the control cohort. On the other hand, loss of Noxa decreased melanoma incidence, delayed melanomagenesis and decreased number of melanomas compared to the controls and Puma -/- cohorts. Upon establishment, melanomas in the Noxa -/- mice, grew relatively slower compared to melanomas in the control and Puma -/- cohorts.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/8812
dc.language.isoenen_US
dc.publisherUniversiti Sains Malaysiaen_US
dc.subjectDefeciancy of Puma and Noxa for melanomagenesisen_US
dc.subjectin a mouse model of melanomaen_US
dc.titleDefeciancy Of Puma And Noxa For Melanomagenesis In A Mouse Model Of Melanomaen_US
dc.typeThesisen_US
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