Loss of SMAD4 Is Sufficient to Promote Tumorigenesis in a Model of Dysplastic Barrett's Esophagus

Jovana R Gotovac; Tanjina Kader; Julia Milne; Kenji M Fujihara; Luis E Lara-Gonzalez; Kylie L Gorringe; Sangeetha N Kalimuthu; Madawa W Jayawardana; Cuong P Duong; Wayne A Phillips; Nicholas J Clemons

Journal article

Loss of SMAD4 Is Sufficient to Promote Tumorigenesis in a Model of Dysplastic Barrett's Esophagus

Jovana R Gotovac, Tanjina Kader, Julia Milne, Kenji M Fujihara, Luis E Lara-Gonzalez, Kylie L Gorringe, Sangeetha N Kalimuthu, Madawa W Jayawardana, Cuong P Duong, Wayne A Phillips, Nicholas J Clemons

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY | ELSEVIER INC | Published : 2021

DOI: 10.1016/j.jcmgh.2021.03.008

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Abstract

BACKGROUND & AIMS: Esophageal adenocarcinoma (EAC) develops from its precursor Barrett's esophagus through intermediate stages of low- and high-grade dysplasia. However, knowledge of genetic drivers and molecular mechanisms implicated in disease progression is limited. Herein, we investigated the effect of Mothers against decapentaplegic homolog 4 (SMAD4) loss on transforming growth factor β (TGF-β) signaling functionality and in vivo tumorigenicity in high-grade dysplastic Barrett's cells. METHODS: An in vivo xenograft model was used to test tumorigenicity of SMAD4 knockdown or knockout in CP-B high-grade dysplastic Barrett's cells. RT2 polymerase chain reaction arrays were used to analyze ..

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University of Melbourne Researchers

Kylie Gorringe Author The Sir Peter Maccallum Department of Oncology

Wayne Phillips Author The Sir Peter Maccallum Department of Oncology

Nicholas Clemons Author The Sir Peter Maccallum Department of Oncology

Cuong Duong Author Surgery - St Vincent's Hospital

Madawa Jayawardana Author The Sir Peter Maccallum Department of Oncology

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Grants

Awarded by National Health and Medical Research Council of Australia

Awarded by Department of Health and Human Services acting through the Victorian Cancer Agency, Victoria, Australia

Funding Acknowledgements

This research was supported by National Health and Medical Research Council of Australia Project grant APP1120293 (W.A.P. and N.J.C.) and Ideas grant APP1182525 (N.J.C). Also supported by a Melbourne International Research Scholarship (University of Melbourne) (J.R.G.), and Fellowship MCRF16002 from the Department of Health and Human Services acting through the Victorian Cancer Agency, Victoria, Australia (N.J.C.).