Multidrug resistance gene and P-glycoprotein expression in gastric adenocarcinoma and precursor lesions.
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 energy-dependent 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 tumour. 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.
Department de Gastroenterologia, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago.
V
V
Vollrath
J
J
Chianale
S
S
Gonzalez
I
I
Duarte
L
L
Andrade
L
L
Ibañez
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000230:Adenocarcinoma / Q000235:genetics*; D003106:Colon / Q000473:pathology; D004351:Drug Resistance / Q000235:genetics*; D005753:Gastric Mucosa / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000235:genetics*; D008679:Metaplasia; D009693:Nucleic Acid Hybridization; D011230:Precancerous Conditions / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000235:genetics*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger