Multidrug resistance gene and P-glycoprotein expression in gastric adenocarcinoma and precursor lesions |
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Authors: | Valeska Vollrath Jose Chianale Sergio Gonzalez Ignacio Duarte Leonardo Andrade Luis Ibañez |
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Institution: | 1. Departamentos de Gastroenterologia y Anatomia Patologica, Facultad Medicina, Pontificia Universidad Catolica de Chile, 114-D, Casilla, Santiago, Chile 2. Facultad de Medicina, Pontificia Universidad Catolica de Chile, Chile
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Abstract: | Overexpression of the Multiple Drug Resistance gene (MDR1) has been proposed as a major mechanism related to both intrinsic
and acquired resistance to chemotherapeutic agents. The gene product is a membrane protein (P-glycoprotein), that acts as
an energydependent drug efflux pump decreasing drug accumulation in resistant tumor cells. We have characterized MDR1 and
P-Glycoprotein expression in human gastric adenocarcinoma and in precursor lesions. MDR1 mRNAs, analyzed by dot-blot technique,
were detected in 9 of 10 non-tumoral gastric mucosae and in 8 of 10 gastric adenocarcinomas. Immunohistochemical analysis,
using the MRK16 monoclonal antibody, revealed heterogeneous expression of P-Glycoprotein in individual cells. The P-Glycoprotein
was found on the surface of cells of gastric areas with intestinal metaplasia subtype III. This type of intestinal metaplasia,
also called “colonic metaplasia”, has been strongly associated with a high risk for the development of gastric cancer. The
fact that the P-Glycoprotein was detected in this precursor lesion is consistent with the intestinal metaplasia dysplasia
and carcinoma sequence proposed in the histogenesis of this tumor. The finding that P-Glycoprotein was heterogeneously expressed
in malignant cells of some gastric adenocarcinomas also suggests that this transporter system probably contributes to primary
and secondary multidrug resistance in this neoplasm. |
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Keywords: | Multidrug resistance gene P-glycoprotein Gastric cancer |
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