Establishing causality for Cdkn2a loss in liver progenitor cell transformation as a mechanism for hepatocarcinogenesis

Robyn Patricia Strauss

doi:10.4225/23/59fa95d0fe7ba

Establishing causality for Cdkn2a loss in liver progenitor cell transformation as a mechanism for hepatocarcinogenesis

Robyn Patricia Strauss

School of Molecular Sciences

Research output: Thesis › Doctoral Thesis

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Abstract

The CDKN2A gene is frequently mutated or methylated in Hepatocellular carcinomas. Indeed, we observed the two tumour suppressors encoded by CDKN2A, ARF and INK4A, were consistently diminished following the tumorigenic transformation of putative liver cancer stem cell, liver progenitor cells (LPCs). This thesis examined the causality of CDKN2A loss in murine LPC transformation utilising multiple in vitro and in vivo approaches. The data presented provide compelling evidence that the loss of ARF and INK4A enhances the propensity of LPCs to undergo a tumorigenic transformation and affects liver homeostasis.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	The University of Western Australia
Supervisors/Advisors	Callus, Bernard, Supervisor Yeoh, George, Supervisor
Award date	24 Oct 2017
DOIs	https://doi.org/10.4225/23/59fa95d0fe7ba
Publication status	Unpublished - 2017

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SDG 3 Good Health and Well-being

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10.4225/23/59fa95d0fe7ba

THESIS - DOCTOR OF PHILOSOPHY - STRAUSS Robyn Patricia - 2017
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title = "Establishing causality for Cdkn2a loss in liver progenitor cell transformation as a mechanism for hepatocarcinogenesis",

abstract = "The CDKN2A gene is frequently mutated or methylated in Hepatocellular carcinomas. Indeed, we observed the two tumour suppressors encoded by CDKN2A, ARF and INK4A, were consistently diminished following the tumorigenic transformation of putative liver cancer stem cell, liver progenitor cells (LPCs). This thesis examined the causality of CDKN2A loss in murine LPC transformation utilising multiple in vitro and in vivo approaches. The data presented provide compelling evidence that the loss of ARF and INK4A enhances the propensity of LPCs to undergo a tumorigenic transformation and affects liver homeostasis.",

keywords = "Liver progenitor cells, Hepatocellular carcinoma, Cdkn2a, ARF, INK4A, Tumorigenesis, Cell culture, Carcinogenesis",

author = "Strauss, \{Robyn Patricia\}",

year = "2017",

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language = "English",

school = "The University of Western Australia",

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TY - BOOK

T1 - Establishing causality for Cdkn2a loss in liver progenitor cell transformation as a mechanism for hepatocarcinogenesis

AU - Strauss, Robyn Patricia

PY - 2017

Y1 - 2017

N2 - The CDKN2A gene is frequently mutated or methylated in Hepatocellular carcinomas. Indeed, we observed the two tumour suppressors encoded by CDKN2A, ARF and INK4A, were consistently diminished following the tumorigenic transformation of putative liver cancer stem cell, liver progenitor cells (LPCs). This thesis examined the causality of CDKN2A loss in murine LPC transformation utilising multiple in vitro and in vivo approaches. The data presented provide compelling evidence that the loss of ARF and INK4A enhances the propensity of LPCs to undergo a tumorigenic transformation and affects liver homeostasis.

AB - The CDKN2A gene is frequently mutated or methylated in Hepatocellular carcinomas. Indeed, we observed the two tumour suppressors encoded by CDKN2A, ARF and INK4A, were consistently diminished following the tumorigenic transformation of putative liver cancer stem cell, liver progenitor cells (LPCs). This thesis examined the causality of CDKN2A loss in murine LPC transformation utilising multiple in vitro and in vivo approaches. The data presented provide compelling evidence that the loss of ARF and INK4A enhances the propensity of LPCs to undergo a tumorigenic transformation and affects liver homeostasis.

KW - Liver progenitor cells

KW - Hepatocellular carcinoma

KW - Cdkn2a

KW - ARF

KW - INK4A

KW - Tumorigenesis

KW - Cell culture

KW - Carcinogenesis

U2 - 10.4225/23/59fa95d0fe7ba

DO - 10.4225/23/59fa95d0fe7ba

M3 - Doctoral Thesis

ER -

Establishing causality for Cdkn2a loss in liver progenitor cell transformation as a mechanism for hepatocarcinogenesis

Abstract

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