[Analysis of differentiation characters in osteosarcoma Mdr sublines].
OBJECTIVE
To explore the relationship between multidrug resistance (Mdr) and malignancy. To observe whether P-glycoprotein (P-gp) overexpression had the same bioactivity as osteogenic stem cell turning into more mature cell or more complex phenotype when parent cell line turned to Mdr phenotype.


METHODS
Six cell sublines of Mdr phenotype with different expression degree were analyzed. Stathmin generally identified in malignancy cell and stem cell, was a microtubule associated protein and the signal of differentiation in osteogenic stem cell. RT-PCR and hybridization in situ were used to analyze the relationship between Mdr1 mRNA and expression of Stathmin mRNA and VEGF mRNA.


RESULTS
Morphological and functional analysis of Mdr phenotype showed the P-gp-positive cell lines were more differentiated than the parent cells in terms of enhanced activity of cellular alkaline phosphatase. These subclones all displayed a decrease in potential malignancy such as tumor growth rate and metastatic ability. A significant negative correlation could be identified between Mdr1 mRNA and expression of VEGF and Stathmin mRNA.


CONCLUSIONS
Expression of Mdr1/P170 indicated osteosarcoma cells differentiated towards more mature state, which will develop the new research field of Mdr and supply the new research method of the function of P- gp.
Zeng
Heng
H
Department of Orthopaedics, Tongji Hospital Affiliated of Tongji Medical College, Huazhong University of Science and Technology,Wuhan 430030, Hubei, China. zengheng@hotmail.com
Chen
An-Min
AM
Li
Feng
F
Yang
Cai-Hong
CH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D042461:Vascular Endothelial Growth Factor A; C467484:VEGFA protein, human