Expression of drug resistance gene products during progression of lung carcinomas.
In order to study whether the presence of mechanisms of drug resistance is a characteristic unique to advanced lung cancer or occurs already early in the course of the disease, we investigated the expression of gluathione S-transferase-pi (GST-pi), P-glycoprotein (P-gp) and metallothionein (MT) in 80 human lung carcinomas and in 20 normal lung tissues using immunohistochemistry. We found that all three proteins were expressed in resected normal lung and lung carcinomas. Expression of GST-pi and MT was elevated in tumor tissues in comparison to normal lung tissues, whereas P-gp was highly expressed in normal lung. GST-pi and MT expression increased with increasing tumor volume and differentiation grade. These results suggest that the level of GST-pi and MT in lung cells increases as cells progress from the normal to the transformed state and that drug resistance gene products are already present in lung carcinomas at the time of surgical resection.
Mattern
Jürgen
J
German Cancer Research Center, Department E0600, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. j.mattern@dkfz.de
Koomägi
Reet
R
Volm
Manfred
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D018450:Disease Progression; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D008668:Metallothionein / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D007527:Isoenzymes; D008668:Metallothionein; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase