Open AccessExpression and Functions of P‐glycoprotein ( mdr 1 gene product) in Normal and Malignant Tissues
Author(s) -
Sugawara Isamu
Publication year - 1990
Publication title -
acta patholigica japonica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
ISSN - 0001-6632
DOI - 10.1111/j.1440-1827.1990.tb01598.x
Subject(s) - glycoprotein , pathology , p glycoprotein , gene , gene product , medicine , gene expression , cancer research , biology , microbiology and biotechnology , genetics , multiple drug resistance , antibiotics
This paper describes the cellular and tissue distribution of P‐glycoprotein (P‐GP) (mdrl gene product), the role of P‐GP in vivo and immunodiagnosis of multi‐drug‐resistant cancers. We mainly used MRK 16 monoclonal antibody (MAb) reactive with P‐GP. P‐GP was found to be expressed very strongly in the adrenal cortex of adults and strongly in the renal tubules of the kidney, capillary blood vessels of the brain, and also in placenta. Interestingly, P‐GP was not distributed in fetal and neonatal adrenals, and thus may be closely related to adrenal maturation. A high level of P GP expression was also seen in all cases of functional hormone producing adrenal tumor, one case of insulinoma, two cases of untreated colonic cancer, one case each of untreated lung cancer, gastric cancer and breast cancer, six cases of renal cell carcinoma and 17 cases of bladder cancer. Using flow cytometry and immunocytochemistry, we investigated the reactivity of MRK 16 MAb with peripheral human mononuclear cells (mainly blastic cells and lymphocytes) from 31 patients with leukemia or malignant lymphoma. Reactivity with MRK 16 MAb was observed in five cases. Some cases reflected the prior administration of adriamycin, vincristine and VP 16, which are known to induce P GP expression. P GP MRK 16 protein A‐Sepha‐rose complex derived from human adrenal possessed marked ATPase activity. These data suggest that P‐GP may play a physiological role in the human adrenal. Finally, diagnostic criteria of multi‐drug‐resistant cancers are presented.