title: Distinct Biochemical Pools of Golgi Phosphoprotein 3 in the Human Breast Cancer Cell Lines MCF7 and MDA-MB-231.
abstract: Golgi phosphoprotein 3 (GOLPH3) has been implicated in the development of carcinomas in many human tissues, and is currently considered a bona fide oncoprotein. Importantly, several tumor types show overexpression of GOLPH3, which is associated with tumor progress and poor prognosis. However, the underlying molecular mechanisms that connect GOLPH3 function with tumorigenicity are poorly understood. Experimental evidence shows that depletion of GOLPH3 abolishes transformation and proliferation of tumor cells in GOLPH3-overexpressing cell lines. Conversely, GOLPH3 overexpression drives transformation of primary cell lines and enhances mouse xenograft tumor growth in vivo. This evidence suggests that overexpression of GOLPH3 could result in distinct features of GOLPH3 in tumor cells compared to that of non-tumorigenic cells. GOLPH3 is a peripheral membrane protein mostly localized at the trans-Golgi network, and its association with Golgi membranes depends on binding to phosphatidylinositol-4-phosphate. GOLPH3 is also contained in a large cytosolic pool that rapidly exchanges with Golgi-associated pools. GOLPH3 has also been observed associated with vesicles and tubules arising from the Golgi, as well as other cellular compartments, and hence it has been implicated in several membrane trafficking events. Whether these and other features are typical to all different types of cells is unknown. Moreover, it remains undetermined how GOLPH3 acts as an oncoprotein at the Golgi. Therefore, to better understand the roles of GOLPH3 in cancer cells, we sought to compare some of its biochemical and cellular properties in the human breast cancer cell lines MCF7 and MDA-MB-231 with that of the non-tumorigenic breast human cell line MCF 10A. We found unexpected differences that support the notion that in different cancer cells, overexpression of GOLPH3 functions in diverse fashions, which may influence specific tumorigenic phenotypes.
authors.affiliation: Department of Physiology, School of Medicine, and Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: María J
authors.initials: MJ
authors.lastname: Tenorio
authors.affiliation: Department of Physiology, School of Medicine, and Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Breyan H
authors.initials: BH
authors.lastname: Ross
authors.affiliation: Department of Physiology, School of Medicine, and Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Luchsinger
authors.affiliation: Department of Physiology, School of Medicine, and Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Andrés
authors.initials: A
authors.lastname: Rivera-Dictter
authors.affiliation: Department of Physiology, School of Medicine, and Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Arriagada
authors.affiliation: Department of Physiology, School of Medicine, and Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Diego
authors.initials: D
authors.lastname: Acuña
authors.affiliation: Department of Physiology, School of Medicine, and Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Aguilar
authors.affiliation: Department of Physiology, School of Medicine, and Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Viviana
authors.initials: V
authors.lastname: Cavieres
authors.affiliation: Department of Physiology, School of Medicine, and Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Patricia V
authors.initials: PV
authors.lastname: Burgos
authors.affiliation: Department of Anatomy, Histology and Pathology, School of Medicine, and Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ehrenfeld
authors.affiliation: Department of Physiology, School of Medicine, and Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Gonzalo A
authors.initials: GA
authors.lastname: Mardones
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000096:biosynthesis; D005260:Female; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D051381:Rats; D014183:Transplantation, Heterologous; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; C429024:GOLPH3 protein, human; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; C037178:phosphatidylinositol 4-phosphate; D019870:1-Phosphatidylinositol 4-Kinase