We recently reported that multidrug-resistant, P-170 glycoprotein-positive, Adriamycin-selected, human breast tumor (MCF7/ADRR) cells were resistant to the benzoquinonoid ansamycin antibiotics geldanamycin (GL) and herbimycin A (HA) and that significantly fewer hydroxyl radicals were formed in resistant cells.
To measure ABCB1 function in tumors, we performed PET experiments using both [<sup>18</sup>F]AVT-011 and [<sup>18</sup>F]FDG in mice bearing orthotopic breast tumors (n = 7-10/group) expressing clinically relevant levels of ABCB1.
In this pilot study, MDR1 expression in primary breast tumors was inversely related with the efficacy of first-line chemotherapy, and high expression level was a significant predictor of poor prognosis for patients with advanced disease.
Reduced ABCB1 protein levels in breast tumors was associated with triple-negative subtype (adjusted odds ratio [OR<sub>adj</sub>] =0.24; 95% confidence interval [CI] =0.13-0.45), lymph node status < pN2 (OR<sub>adj</sub> =0.27; 95% CI =0.10-0.71), tumor size >2 cm (OR<sub>adj</sub> =0.55; 95% CI =0.32-0.93), and hypertensive status (OR<sub>adj</sub> =0.42; 95% CI =0.24-0.73), and it was significantly associated with shorter disease-free survival, either for all breast cancer patients (<i>p</i> log-rank =0.012; hazard ratio [HR] =3.46; 95% CI =1.21-9.91) or for those with triple-negative tumors (<i>p</i> log-rank =0.007; HR =11.41; 95% CI =1.29-100.67).
In this study, the mechanism of 99mTc-sestamibi uptake by nine human breast tumor cell lines was analyzed as a function of P-glycoprotein (PgP) expression.
Taken together, our data indicate that breast tumors with alveolar structures possess resistance to NAC, which is not related to high expression of MDR genes, whereas chemoresistance of tumors with trabecular structures can depend on the expression level of ABCB1.
An important result of our study is the demonstration of a correlation between P-gp expression and patients with HER2-positive breast tumors that do not express steroid receptors.
Subsequently, there is a significant decrease in both MDR1 and Bcl-x(L) gene expression and an enhancement in caspase-3 activity and chemosensitivity in the breast tumor cells.
The quantitative real-time polymerase chain reaction (Q-RT-PCR) technique was used to assess the MDR1 and MMP2 RNA expression levels in primary breast tumor and lymph nodal specimens.
Immunohistochemistry confirmed that breast carcinoma cells lackedP-glycoprotein expression; however, interstitial mononuclear cells, morphologically consistent with lymphocytes or macrophages did show immunostaining in some of these breast tumors.
MDR1/gp170 expression has been studied in breast cancer, but the prevalence of this expression and its role in breast tumor drug resistance are unclear.
P-Glycoprotein RNA expression was positive in eight of 23 lymphomas and two of 12 colon tumors; however, many other normal and malignant tissues, including lung, bladder, and breast tumors, had low or undetectable levels of P-glycoprotein RNA expression.
However, transcripts derived from the MDR1 USP were detected in some drug-resistant cell lines and a high proportion of primary breast tumors (71.6%; n = 61), whereas they were present at low frequency in normal breast tissue (10%; n = 10).
The expression of MDR in breast tumors is related to their origination from a tissue that constitutively expresses Pgp as well as to the development of resistance during successive courses of chemotherapy.
The regulatory effect of Gal-1 on multidrug resistance (MDR) breast cancer cells is still unclear. qRT-PCR and western blot showed that Gal-1 and MDR gene 1 (MDR1) were both highly expressed in breast tumor tissues and cell lines.