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LAT1 is a putative therapeutic target in endometrioid endometrial carcinoma.
Marshall, Amy D; van Geldermalsen, Michelle; Otte, Nicholas J; Anderson, Lyndal A; Lum, Trina; Vellozzi, Melissa A; Zhang, Blake K; Thoeng, Annora; Wang, Qian; Rasko, John E J; Holst, Jeff.
Afiliación
  • Marshall AD; Gene and Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, New South Wales, Australia.
  • van Geldermalsen M; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
  • Otte NJ; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
  • Anderson LA; Origins of Cancer Program, Centenary Institute, University of Sydney, Camperdown, New South Wales, Australia.
  • Lum T; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
  • Vellozzi MA; Origins of Cancer Program, Centenary Institute, University of Sydney, Camperdown, New South Wales, Australia.
  • Zhang BK; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
  • Thoeng A; Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
  • Wang Q; Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
  • Rasko JE; Gene and Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, New South Wales, Australia.
  • Holst J; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Int J Cancer ; 139(11): 2529-39, 2016 12 01.
Article en En | MEDLINE | ID: mdl-27486861
l-type amino acid transporters (LAT1-4) are expressed in various cancer types and are involved in the uptake of essential amino acids such as leucine. Here we investigated the expression of LAT1-4 in endometrial adenocarcinoma and evaluated the contribution of LATs to endometrial cancer cell growth. Analysis of human gene expression data showed that all four LAT family members are expressed in endometrial adenocarcinomas. LAT1 was the most highly expressed, and showed a significant increase in both serous and endometrioid subtypes compared to normal endometrium. Endometrioid patients with the highest LAT1 levels exhibited the lowest disease-free survival. The pan-LAT inhibitor BCH led to a significant decrease in cell growth and spheroid area in four endometrial cancer cell lines tested in vitro. Knockdown of LAT1 by shRNA inhibited cell growth in HEC1A and Ishikawa cells, as well as inhibiting spheroid area in HEC1A cells. These data show that LAT1 plays an important role in regulating the uptake of essential amino acids such as leucine into endometrial cancer cells. Increased ability of BCH compared to LAT1 shRNA at inhibiting Ishikawa spheroid area suggests that other LAT family members may also contribute to cell growth. LAT1 inhibition may offer an effective therapeutic strategy in endometrial cancer patients whose tumours exhibit high LAT1 expression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Endometriales / Carcinoma Endometrioide / Transportador de Aminoácidos Neutros Grandes 1 Límite: Female / Humans Idioma: En Revista: Int J Cancer Año: 2016 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Endometriales / Carcinoma Endometrioide / Transportador de Aminoácidos Neutros Grandes 1 Límite: Female / Humans Idioma: En Revista: Int J Cancer Año: 2016 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos