Flowcytometric analysis of multidrug-resistance-associated antigen (P-Glycoprotein) and DNA ploidy in human colon cancer

Marco Danova, Monica Giordano, Eugenio Erba, Sergio Palmeri, Vincenza Candiloro, Alberto Riccardi, Giovanni Ucci, Giuliano Mazzini, Maurizio D'Incalci, Edoardo Ascari

Research output: Contribution to journalArticle

Abstract

In many cell systems, resistance to cytotoxic drugs is acquired by the amplification and/or overexpression of the multidrug resistance (mdr) gene, which codes for the glycoprotein, p170 (P-glycoprotein). Moreover, in a variety of malignant tumours there is increasing evidence of the relationship between the DNA ploidy pattern of patients and their prognosis. In this study we aimed to evaluate these two potential indicators of constitutive drug resistance in human colorectal tumours. We employed a method to quantify simultaneously, on a per cell basis, mdr gene expression (using the C219 monoclonal antibody for P-glycoprotein) and nuclear DNA content with high-resolution bivariate flow cytometry. The study was performed on a human coloncarcinoma-derived cell line (LoVo) and its doxorubicinresistant variant (LoVo/Dx) and on tumour samples and adjacent normal mucosa from 35 untreated patients with colon cancer. The P-glycoprotein was found in both LoVo and LoVo/Dx cells with levels slightly lower in the parental than in the resistant subline (P, NS). A multidrug-resistant specific probe for mRNA expression and Western blot assay confirmed the specificity of p170 expression. All of the colon cancer with unimodal diploid DNA distribution and all the normal colonic mucosa samples showed P-glycoprotein expression, without a statistically significant difference in median values between tumours and normal samples. Tumours with bimodal DNA distribution showed median values of P-glycoprotein expression of their hyperdiploid cell clones significantly higher than those of their diploid clones and of the tumours with unimodal DNA distribution (P

Original languageEnglish
Pages (from-to)575-580
Number of pages6
JournalJournal of Cancer Research and Clinical Oncology
Volume118
Issue number8
DOIs
Publication statusPublished - Aug 1992

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Ploidies
Multiple Drug Resistance
P-Glycoprotein
Colonic Neoplasms
Antigens
DNA
MDR Genes
Neoplasms
Diploidy
Mucous Membrane
Clone Cells
Polyploidy
Normal Distribution
Drug Resistance
Colorectal Neoplasms
Glycoproteins
Flow Cytometry
Western Blotting
Monoclonal Antibodies
Gene Expression

Keywords

  • Colon cancer
  • DNA ploidy
  • Flow cytometry
  • Multidrug resistance
  • P-glycoprotein

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Flowcytometric analysis of multidrug-resistance-associated antigen (P-Glycoprotein) and DNA ploidy in human colon cancer. / Danova, Marco; Giordano, Monica; Erba, Eugenio; Palmeri, Sergio; Candiloro, Vincenza; Riccardi, Alberto; Ucci, Giovanni; Mazzini, Giuliano; D'Incalci, Maurizio; Ascari, Edoardo.

In: Journal of Cancer Research and Clinical Oncology, Vol. 118, No. 8, 08.1992, p. 575-580.

Research output: Contribution to journalArticle

Danova, Marco ; Giordano, Monica ; Erba, Eugenio ; Palmeri, Sergio ; Candiloro, Vincenza ; Riccardi, Alberto ; Ucci, Giovanni ; Mazzini, Giuliano ; D'Incalci, Maurizio ; Ascari, Edoardo. / Flowcytometric analysis of multidrug-resistance-associated antigen (P-Glycoprotein) and DNA ploidy in human colon cancer. In: Journal of Cancer Research and Clinical Oncology. 1992 ; Vol. 118, No. 8. pp. 575-580.
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