By hybridization of cancer profile arrays, we found that Che-1 expression is strongly down-regulated in several tumors, including colon and kidney carcinomas, compared with the relative normal tissues.
In contrast to carcinomas, BRCA1-deficient mouse carcinosarcomas resembling MBC show intrinsic resistance to olaparib caused by increased P-glycoprotein (Pgp) drug efflux transporter expression.
In 59 evaluable patients with primary breast carcinomas, MDR1 RNA levels of the carcinomas were negative in 54%, low in 29% and high in 17% of the patients.
Of eight carcinomas treated by radiotherapy and/or chemotherapy, seven (88%) exhibited MDR1 transcripts as compared with 24 (35%) of 69 untreated carcinomas (Fisher's exact test; P = .01).
A marked significant increase in P-gp expression was observed in recurrent oral carcinomas as compared with normal oral tissues (p < 0.001) and dysplastic lesions (p < 0.01).
Because P-glycoprotein expression might be associated with a more aggressive behaviour of colorectal carcinomas (Weinstein et al., Cancer Res, 1991, 51, 2720-2726), we determined the relationship between MDR1 RNA expression of the carcinomas and the survival of the patients.
Using the DNA fragment from normal tissues rather than KB cells, we have reanalyzed MDR1 mRNA levels in 12 renal carcinomas and 4 colon adenocarcinomas.
This study was designed to measure the MDR1 messenger RNA (mRNA) content of ovarian and lung carcinomas and to analyze clinical correlations of MDR1 expression in these tumors.
Antibody and complementary DNA probes utilized for detection of the MDR1 gene product and mRNA levels, respectively, revealed that prior to drug treatment the lung tumor had virtually no detectable P-glycoprotein while both colon carcinomas displayed low and heterogeneous expression of this resistance-related protein.
Expression of HER-2/neu or mutant p53 was similar in both tumor groups studied--mammary carcinoma with a low basal expression of P-glycoprotein compared with endometrial and cervical carcinomas with significantly (P = .0002; chi-square test) higher levels of expression.
Amplification of the mdr1-gene has been observed in tumor cell lines exposed to cytotoxic drugs; however, significant information is lacking as to whether this holds true in clinical carcinomas.
MDR1 expression was detectable, albeit at low levels, in 8 of the 11 tumors, suggesting a possible role of this gene in the drug resistance of prostate carcinomas.
These results imply that the higher levels of MDR1 mRNA found in well-differentiated carcinomas derived from colorectal tissues are the results of increased expression of the MDR1 gene in the luminal surface cells.
In patients with primary FIGO III carcinomas (n = 18), the overall-survival time (OST) was significantly prolonged with low MDR1/P-gp expression level (P = 0.015).
HT29 MDR-1 negative cells produce undifferentiated signet ring carcinomas when implanted subcutaneously into SCID mice, while HT29 MDR-1 positive cells form tumors with tubular structures, but without signet ring cells.