Electrophoretic analysis of 248 clinical breast cancer specimens for P-glycoprotein overexpression or gene amplification.

1989 ◽  
Vol 7 (8) ◽  
pp. 1129-1136 ◽  
Author(s):  
D E Merkel ◽  
S A Fuqua ◽  
A K Tandon ◽  
S M Hill ◽  
A U Buzdar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Gene Amplification ◽  
Multiple Drug Resistance ◽  
Electrophoretic Analysis ◽  
Gene Copy ◽  
Cross Resistance ◽  
Glycoprotein Gene ◽  
P Glycoprotein ◽  
Clinical Breast

Multiple drug resistance (MDR), consisting of acquired cross resistance to anthracyclines, vinca alkyloids, and other antineoplastic antibiotics, has been described in a variety of cell lines. This MDR phenotype is associated with overexpression and sometimes amplification of a gene coding for a 170 kDa glycoprotein, termed P-glycoprotein. To understand the role of this mechanism in clinical breast cancer, 248 breast cancer specimens representing both untreated primary and refractory relapsing disease were probed for evidence of P-glycoprotein gene amplification or overexpression using Southern, Northern, or Western blot techniques. In no case was an increase in P-glycoprotein gene copy number or expression detected. Though these findings do not necessarily rule out a role for P-glycoprotein in mediating drug resistance in breast cancer, electrophoretic analysis of clinical specimens is unlikely to provide useful predictive information. More sensitive assays must be developed to overcome the difficulties inherent in analyzing heterogenous tissue samples.

The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2)

2000 ◽  
Vol 113 (11) ◽  
pp. 2011-2021 ◽  
Author(s):  
T. Litman ◽  
M. Brangi ◽  
E. Hudson ◽  
P. Fetsch ◽  
A. Abati ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Multiple Drug Resistance ◽  
Human Colon ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Multiple Drug ◽  
Resistant Phenotype ◽  
P Glycoprotein ◽  
Mcf 7

Mechanisms of drug resistance other than P-glycoprotein are of increasing interest as the list of newly identified members of the ABC transport family has grown. We sought to characterize the phenotype of the newly discovered ABC transporter encoded by the mitoxantrone resistance gene, MXR, also known as ABCP1 or BCRP. The pharmacodynamics of mitoxantrone and 12 other fluorescent drugs were evaluated by confocal microscopy in four multidrug-resistant human colon (S1) and breast (MCF-7) cancer cell lines. We utilized two sublines, MCF-7 AdVp3000 and S1-M1-80, and detected overexpression of MXR by PCR, immunoblot assay and immunohistochemistry. These MXR overexpressing sublines were compared to cell lines with P-glycoprotein- and MRP-mediated resistance. High levels of cross-resistance were observed for mitoxantrone, the anthracyclines, bisantrene and topotecan. Reduced levels of mitoxantrone, daunorubicin, bisantrene, topotecan, rhodamine 123 and prazosin were observed in the two sublines with high MXR expression. Neither the P-glycoprotein substrates vinblastine, paclitaxel, verapamil and calcein-AM, nor the MRP substrate calcein, were extruded from MCF-7 AdVp3000 and S1-M1-80 cells. Thus, the multidrug-resistant phenotype due to MXR expression is overlapping with, but distinct from, that due to P-glycoprotein. Further, cells that overexpress the MXR protein seem to be more resistant to mitoxantrone and topotecan than cells with P-glycoprotein-mediated multidrug resistance. Our studies suggest that the ABC half-transporter, MXR, is a potent, new mechanism for conferring multiple drug resistance. Definition of its mechanism of transport and its role in clinical oncology is required.

scholarly journals Chemosensitizing multiple drug resistance of human carcinoma by bicyclol involves attenuated P-glycoprotein, GST-P and Bcl-2

2006 ◽  
Vol 5 (5) ◽  
pp. 536-543 ◽  
Author(s):  
Bing Zhu ◽  
Geng Tao Liu ◽  
Yong Mei Zhao ◽  
Ruo Su Wu ◽  
Samuel J Strada
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Human Carcinoma ◽  
P Glycoprotein

Late relapse associated with CEP 17 polysomic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20011-20011
Author(s):  
L. J. Theobald ◽  
S. Dobin ◽  
S. Beeran ◽  
D. Miltenburg ◽  
H. Rajab ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Amplification ◽  
Tumor Size ◽  
Nodal Status ◽  
Gene Copy ◽  
Categorical Variables ◽  
Late Relapse ◽  
Study Cohort ◽  
Breast Cancers ◽  
Clinicopathologic Factor

20011 Background: The clinicopathologic features associated with chromosome enumeration probe 17 (CEP 17) polysomy by fluorescence in situ hybridization (FISH) are not well defined. CEP 17 polysomy is frequently encountered in assessing Her-2neu amplification, which has become an important adjuvant therapeutic target. One mechanism to increase Her-2neu gene copy is polysomy. In this analysis the prognostic and predictive factors associated with CEP 17 polysomy are compared to similar factors in Her-2neu gene amplification. Methods: All cases of Her-2neu gene amplification and CEP 17 polysomic breast cancers from 2000 to present were abstracted. The polysomy group was defined as at least 3 gene copies and was further subdivided into two groups; 3–4 copies and ≥ 5 copies. This resulted in 193 cases of invasive breast cancer, which became the study cohort. Polysomic status and her-2neu gene amplification was compared to age, estrogen receptor (ER), progesterone receptor (PR), grade, tumor size, cell type, mitotic rate, nodal status, number of positive nodes and relapse. Descriptive statistics were used for categorical variables. The χ2 test was used to compare each clinicopathologic factor. Results: Both the ER and PR status was significantly different in the 3 groups. For the Her-2neu amplified, the polysomic 3–4, and the polysomic ≥ 5, the ER positive status was 53%, 67% and 81%, respectively (p = .012). Histologic grade, tumor size and nodal status were not significantly different between groups. Lobular pathology was present in 15% of the polysomy ≥ 5 group, 8% of the polysomy 3–4 group and 1.7% of the amplified group and this difference was significant (p = .03). Relapse disease status was significantly more frequent in the polysomy ≥ 5 group (18.5%) compared to the amplified group (2.6%) (p = .007). Within the relapsed group the median time to relapse was 4 years for the amplified patients versus 12 years and 10 years for the polysomic patients. Conclusion: The incidence of CEP 17 polysomy varies in the literature from 10–50% depending on definitions. Our study is unique in that we divided the polysomic group into 3–4 copies which can be complicated by proliferative activity versus ≥ 5 copies. A significant association between relapse and polysomic breast cancer is described in our dataset. No significant financial relationships to disclose.

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