Merck
  • Home
  • Search Results
  • Unraveling heterogeneous susceptibility and the evolution of breast cancer using a systems biology approach.

Unraveling heterogeneous susceptibility and the evolution of breast cancer using a systems biology approach.

Genome biology (2015-04-09)
Andrés Castellanos-Martín, Sonia Castillo-Lluva, María Del Mar Sáez-Freire, Adrián Blanco-Gómez, Lourdes Hontecillas-Prieto, Carmen Patino-Alonso, Purificación Galindo-Villardon, Luis Pérez Del Villar, Carmen Martín-Seisdedos, María Isidoro-Garcia, María Del Mar Abad-Hernández, Juan Jesús Cruz-Hernández, César Augusto Rodríguez-Sánchez, Rogelio González-Sarmiento, Diego Alonso-López, Javier De Las Rivas, Begoña García-Cenador, Javier García-Criado, Do Yup Lee, Benjamin Bowen, Wolfgang Reindl, Trent Northen, Jian-Hua Mao, Jesús Pérez-Losada
ABSTRACT

An essential question in cancer is why individuals with the same disease have different clinical outcomes. Progress toward a more personalized medicine in cancer patients requires taking into account the underlying heterogeneity at different molecular levels. Here, we present a model in which there are complex interactions at different cellular and systemic levels that account for the heterogeneity of susceptibility to and evolution of ERBB2-positive breast cancers. Our model is based on our analyses of a cohort of mice that are characterized by heterogeneous susceptibility to ERBB2-positive breast cancers. Our analysis reveals that there are similarities between ERBB2 tumors in humans and those of backcross mice at clinical, genomic, expression, and signaling levels. We also show that mice that have tumors with intrinsically high levels of active AKT and ERK are more resistant to tumor metastasis. Our findings suggest for the first time that a site-specific phosphorylation at the serine 473 residue of AKT1 modifies the capacity for tumors to disseminate. Finally, we present two predictive models that can explain the heterogeneous behavior of the disease in the mouse population when we consider simultaneously certain genetic markers, liver cell signaling and serum biomarkers that are identified before the onset of the disease. Considering simultaneously tumor pathophenotypes and several molecular levels, we show the heterogeneous behavior of ERBB2-positive breast cancer in terms of disease progression. This and similar studies should help to better understand disease variability in patient populations.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium dodecyl sulfate, 92.5-100.5% based on total alkyl sulfate content basis
Sigma-Aldrich
Sodium dodecyl sulfate, BioXtra, ≥99.0% (GC)
Sigma-Aldrich
Cholesterol, powder, BioReagent, suitable for cell culture, ≥99%
Sigma-Aldrich
Sodium dodecyl sulfate, ≥99.0% (GC), dust-free pellets
Sigma-Aldrich
Urea solution, 40 % (w/v) in H2O
Sigma-Aldrich
Magnesium chloride solution, for molecular biology, 1.00 M±0.01 M
Sigma-Aldrich
Magnesium chloride solution, PCR Reagent, 25 mM MgCI2 solution for PCR
Sigma-Aldrich
Sodium chloride solution, 5 M
Sigma-Aldrich
Sodium dodecyl sulfate, ReagentPlus®, ≥98.5% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC)
Sigma-Aldrich
Sodium chloride solution, 0.85%
Supelco
Cholesterol solution, certified reference material, 10 mg/mL in chloroform
Sigma-Aldrich
Sodium dodecyl sulfate, ACS reagent, ≥99.0%
Sigma-Aldrich
Magnesium chloride solution, BioUltra, for molecular biology, 2 M in H2O
Sigma-Aldrich
Urea-12C, 99.9 atom % 12C
Sigma-Aldrich
Sodium chloride, AnhydroBeads, −10 mesh, 99.99% trace metals basis
Sigma-Aldrich
Sodium chloride, AnhydroBeads, −10 mesh, 99.999% trace metals basis
Sigma-Aldrich
Cholesterol, tested according to Ph. Eur.
Sigma-Aldrich
Chlorotrimethylsilane, purified by redistillation, ≥99%
Sigma-Aldrich
Methoxylamine hydrochloride solution, 25-30 wt. % in H2O
Sigma-Aldrich
Methoxyamine hydrochloride, 98%
Sigma-Aldrich
Sodium chloride, random crystals, optical grade, 99.9% trace metals basis
Sigma-Aldrich
Sodium chloride, 99.999% trace metals basis
Sigma-Aldrich
Sodium chloride-35Cl, 99 atom % 35Cl
Sigma-Aldrich
Phenylmethanesulfonyl fluoride, ≥99.0% (T)
Sigma-Aldrich
Chlorotrimethylsilane, produced by Wacker Chemie AG, Burghausen, Germany, ≥99.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, ≥98.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, BioUltra, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
Sodium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
Magnesium chloride solution, BioUltra, for molecular biology, ~0.025 M in H2O