R. Kramer et al., CONSTITUTIVE EXPRESSION OF MULTIDRUG-RESISTANCE IN HUMAN COLORECTAL TUMORS AND CELL-LINES, British Journal of Cancer, 67(5), 1993, pp. 959-968
In this study we report detection of mdr1 gene expression in the liver
metastases of 7/11 patients with colon carcinoma and characterise the
MDR phenotype associated with a panel of 19 human colon carcinoma cel
l lines. Within this panel, mdr1 mRNA biosynthesis and surface localis
ation of Pgp were assessed with respect to MDR functionality where the
cell lines are representative of different clinical stages of tumour
progression, metastatic potential and differentiation. The data indica
tes that constitutive levels of mdr1 mRNA/Pgp expression may not neces
sarily result in the functional expression of the MDR phenotype. While
low levels of mdr1 mRNA/Pgp were detected in 5/8 well differentiated
colon cell lines, only 2/8 were functionally MDR. In contrast, 10/11 m
oderate and poorly differentiated lines expressed mdr1 mRNA/Pgp and of
these, 9/11 were functionally MDR. The phosphorylation status of the
mature 170 kD P-glycoprotein and the surface localisation of this glyc
oprotein showed the strongest correlation with functionality. Analysis
of cell lines for cross-resistance and chemosensitivity profiles agai
nst a battery of chemotherapeutic drugs suggests multiple mechanisms,
in addition to Pgp, contribute to the overall resistance of colorectal
cancer.