DeterminingMDR1/P-glycoprotein expression in breast cancer

Abstract

The mechanism of chemotherapy resistance in breast cancer is unresolved. MDR1/P‐glycoprotein (P‐Gp) over‐expression confers multidrug resistance in vitro and might play a role in clinical breast cancer. Studies using clinical samples have yielded conflicting results. MDR1/P‐Gp mRNA expression was determined relative to the expression in normal human liver using TaqMan real‐time RT‐PCR (corrected for expression of the housekeeping gene PBGD). Immunohistochemistry (IHC) was performed with monoclonal antibodies against P‐Gp (JSB1, C219). The positive control was SW1573/2R160, the intermediate control SW1573 and the negative control GLC4/ADR. We assayed 9 breast‐cancer cell lines by RT‐PCR and IHC, 52 carcinoma samples by RT‐PCR and 168 samples by IHC. SW1573/2R160 contained high levels of MDR1/P‐Gp mRNA (1.0, equal to liver) and showed strong membranous staining. Expression of MDR1/P‐Gp mRNA in SW1573 (0.05) and GLC4/ADR (3.2 × 10–5) was not detectable by IHC. Very low levels of MDR1/P‐Gp mRNA were measured in breast‐cancer cell lines (mean 3.1 × 10–4, range 1 to 12 × 10–4), but P‐Gp was not detected by IHC. In 25 specimens from chemotherapy‐naive patients, MDR1/P‐Gp mRNA levels varied from 1 to 11 × 10–2 (mean 3.9 × 10–2). In sections of 80 chemotherapy‐naive tumors, no membrane‐bound staining was observed in the tumor cells. Tumors of 27 anthracycline‐treated patients had comparable MDR1/P‐Gp mRNA expression levels (mean 5.4 × 10–2). P‐Gp was undetectable in 88 tumor samples of patients who had received anthracycline‐based chemotherapy. In breast cancer, MDR1/P‐Gp mRNA is low or absent and P‐Gp levels in cancer cells are too low to detect by IHC. Chemotherapy exposure does not result in detectable MDR1/P‐Gp over‐expression. © 2001 Wiley‐Liss, Inc.

Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2)

“…Immunohistochemical studies confirmed undetectable expression of BCRP in breast tumors, even in biopsies from women relapsing after doxorubicin-based chemotherapy (Faneyte et al, 2002).…”

“…Normal tissues without detectable BCRP expression included endometrial cells and squamous epithelial cells in the skin or esophagus. BCRP is variably expressed by immunohistochemistry in normal breast epithelium and blood vessels (Faneyte et al, 2002). Low or undetectable BCRP expression in human and murine lung were also observed by immunohistochemical studies .…”

Multidrug Resistance: Retrospect and Prospects in Anti-Cancer Drug Treatment

“…Although BCRP was originally cloned from a human breast cancer cell line, its level of expression in clinical breast cancer samples was low, as measured using RT-PCR techniques [140], or undetectable when immunohistochemical techniques were applied [141]. However, in a large study encompassing 150 tumours from 21 different cancer types, BCRP expression was detected in over 40% of the tumours examined, with strong expression in gastric carcinoma, hepatocellular carcinoma, endometrial carcinoma, colon cancer, small cell lung cancer and melanoma [142].…”

Mechanisms of resistance to topoisomerase I-targeting drugs

“…BCRP seems to be expressed at low levels in breast cancer cells as well as leukemic cells (Ross et al, 2000;Kanzaki et al, 2001). Furthermore, the expression of BCRP in breast carcinoma cells does not seem to correlate with response to doxorubicin-based chemotherapy (Kanzaki et al, 2001), nor is it upregulated in patients with breast cancer that were previously treated with anthracyclines versus those patients that were not treated with these drugs (Faneyte et al, 2002). Another recent study found that BCRP protein expression was increased in leukemia cells from three out of four patients following an infusion of topotecan and arabinoside-C .…”