Expression profiling of osteosarcoma cells transfected with MDR1 and NEO genes: Regulation of cell adhesion, apoptosis, and tumor suppression-related genes

Marta Sanchez-Carbayo, Thomas J. Belbin, Katia Scotlandi, Michael B. Prystowsky, Nicola Baldini, Geoffrey J. Childs, Carlos Cordon-Cardo

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Abstract

The expression patterns of the osteosarcoma cell line U-2 OS, and three derived subclones containing stably transfected MDR1, NEO and MDR1/NEO genes were compared using cDNA microarrays comprising 8976 known genes and expressed sequenced tags. Data provided new insights into three critical issues. First, MDR1 overexpression was associated with altered expression of genes related to several cellular pathways, including (a) drug influx/efflux (eg, dynamin 3), (b) metabolic enzymes (eg, monoamine oxidase A), (c) cell adhesion (eg, EPCAM), (d) apoptotic signaling (eg, I-TRAF), (e) senescence (eg, telomerase RNA binding protein staufen), (f) tumor suppression-related genes (eg, KISS-1 and ephrin B3), and (g) immune system receptors (eg, LENG2). MDR1, EPCAM, and ephrin B3 expression was confirmed by immunohistochemistry. Second, MDR1 transfected cells selected with either doxorubicin or neomycin showed distinct expression profiles that could be related to differential selection. Moreover, hierarchical clustering indicated that cells transfected with MDR1 alone, or cotransfected with NEO, displayed more closely related expression profiles than cells transfected only with NEO. Third, transfection with NEO and selection with neomycin produced a considerable number of expression changes within the cell. This study further elucidates the genetic events associated with MDR1 expression and identifies novel targets associated with multidrug resistance.

Original languageEnglish (US)
Pages (from-to)507-517
Number of pages11
JournalLaboratory Investigation
Volume83
Issue number4
StatePublished - Apr 1 2003

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Osteosarcoma
Cell Adhesion
Ephrin-B3
Apoptosis
Neomycin
Dynamin III
Genes
Neoplasms
RNA-Binding Proteins
Monoamine Oxidase
Multiple Drug Resistance
Oligonucleotide Array Sequence Analysis
Doxorubicin
Transfection
Cluster Analysis
Immune System
Immunohistochemistry
Gene Expression
Cell Line
Enzymes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Expression profiling of osteosarcoma cells transfected with MDR1 and NEO genes : Regulation of cell adhesion, apoptosis, and tumor suppression-related genes. / Sanchez-Carbayo, Marta; Belbin, Thomas J.; Scotlandi, Katia; Prystowsky, Michael B.; Baldini, Nicola; Childs, Geoffrey J.; Cordon-Cardo, Carlos.

In: Laboratory Investigation, Vol. 83, No. 4, 01.04.2003, p. 507-517.

Research output: Contribution to journalArticle

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