P-glycoprotein expression in locally advanced breast cancer treated by neoadjuvant chemotherapy

Dixon, A. R.; Bell, Jane M.; Ellis, Ian O.; Elston, C. W.; Blamey, R. W.

doi:10.1038/bjc.1992.309

Cited by 17 publications

(2 citation statements)

References 19 publications

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“…In fact, the largest study so far conducted reported no detectable Pgp expression in 248 consecutive samples [16]. However, after repeated rounds of chemotherapy with a Pgp substrate agent such as doxorubicin, expression of Pgp was detected in 62 % of all specimens examined [8,12,28]. The acquisition of a drug resistance phenotype is one of the primary reasons for the loss of responsiveness in late-stage tumours.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of mitomycin C and doxorubicin on P-glycoprotein expression

Maitra

Halpin

Karlson

et al. 2001

Biochemical Journal

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Previous studies have demonstrated that mitomycin C (MMC) and other DNA cross-linking agents can suppress MDR1 (multidrug resistance 1) gene expression and subsequent functional P-glycoprotein (Pgp) expression, whereas doxorubicin and other anthracyclines increase MDR1 gene expression. In the present study, with stably transfected Madin–Darby canine kidney C7 epithelial cells expressing a human Pgp tagged with green fluorescent protein under the proximal human MDR1 gene promoter, we demonstrated that MMC and doxorubicin have differential effects on Pgp expression and function. Doxorubicin caused a progressive increase in the cell-surface expression of Pgp and function. In contrast, MMC initially increased plasma membrane expression and function at a time when total cellular Pgp was constant and Pgp mRNA expression had been shown to be suppressed. This was followed by a rapid and sustained decrease in cell-surface expression at later times, presumably as a consequence of the initial decrease in mRNA expression. These studies imply that there are at least two independent chemosensitive steps that can alter Pgp biogenesis: one at the level of mRNA transcription and the other at the level of Pgp trafficking. Understanding the combined consequences of these two mechanisms might lead to novel chemotherapeutic approaches to overcoming drug resistance in human cancers by altering either Pgp mRNA expression or trafficking to the membrane.

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Section: Discussionmentioning

confidence: 99%

Differential effects of mitomycin C and doxorubicin on P-glycoprotein expression

Maitra

Halpin

Karlson

et al. 2001

Biochemical Journal

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show abstract

“…Because the adjacent normal breast tissue also stained positive for Pgp, it is hard to differentiate whether the drug resistance is intrinsic or induced type. In contrast, Dixon et al (1992) found all breast cancer tissue samples unstained for Pgp after chemotherapy which may be the result of not choosing anthracyclines or taxanes in the treatment.…”

Section: Effects Of Mdr On Clinical Response To Chemotherapymentioning

confidence: 98%

Locally Advanced Breast Cancer: Multidrug Resistance

Atalay

Methods of Cancer Diagnosis, Therapy and Prognosis

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Clinical Relevance of P-Glycoprotein-Related Resistance in Patients with Acute Leukemia

Nüssler¹,

Pelka-Fleischer²,

Zwierzina³

et al. 1997

Acute Leukemias VI

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P-glycoprotein expression in locally advanced breast cancer treated by neoadjuvant chemotherapy

Abstract: SummaryUsing

Cited by 17 publications

References 19 publications

Differential effects of mitomycin C and doxorubicin on P-glycoprotein expression

Differential effects of mitomycin C and doxorubicin on P-glycoprotein expression

Locally Advanced Breast Cancer: Multidrug Resistance

Clinical Relevance of P-Glycoprotein-Related Resistance in Patients with Acute Leukemia

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