Korean J Hematol.  2000 May;35(2):150-161.

Correlation between the Expression Levels of Transforming Growth Factor-beta (TGF-beta) Receptors and Responsiveness to TGF-beta1-Induced Growth Inhibitory Effects in Leukemic Cell Lines

• Jeon JH
• Park BK

Abstract

BACKGROUND: Defects in TGF-beta receptors have been found in a variety of malignant cells, we therefore investigated whether these defects could be also demonstrated in leukemic cells. In addition, we analyzed the relation between TGF-beta receptor expression and responsiveness to TGF-beta-induced growth inhibitory effects.
METHODS
Eleven human leukemic cell lines and two normal cell lines were recruited for the study. To evaluate the expression of TGF-beta receptor type I (RI) and type II (RII), Western blotting analysis was conducted utilizing two kinds of primary antibodies against both RI and RII. Band strength was quantitated with densitometry. Moreover, specific peptides against primary antibodies were employed for competitive inhibition assay. Responsiveness to TGF-beta1 was assessed by [3H] thymidine uptake.
RESULTS
Bands of same molecular size were demonstrated by two different primary antibodies. Peptides against RI or RII antibodies successfully blocked the emergence of RI or RII message, respectively, verifying that former bands represented specific RI or RII. Relative RI levels in leukemic cells except HL-60 compared with CCL-64, normal lung epithelial cells, were in the range of 0.48~1.14. In contrast, relative RII levels, although variable between individual cells, were less than 0.25 in all the leukemic cells. Percents [3H]thymidine uptake of leukemic cells at 10 ng/mL of TGF-beta1 compared with untreated control were widely distributed in the range of 7.7~62.9%. Positive correlation between RII levels and TGF-beta responsiveness was observed (P=0.025).
CONCLUSION
Defective RI expression seems to be rare, however, defective RII expression appears to be rather common in leukemic cells. Positive correlation between RII levels and TGF-beta responsiveness suggests role of defective RII expression in the acquisition of resistance to TGF-beta in leukemic cells.

Keyword

TGF-beta; TGF-beta receptor type I; TGF-beta receptor type II; expression; responsiveness; leukemic cells

MeSH Terms

Antibodies
Blotting, Western
Cell Line*
Densitometry
Epithelial Cells
Humans
Lung
Peptides
Receptors, Transforming Growth Factor beta
Thymidine
Transforming Growth Factor beta
Transforming Growth Factor beta1
Antibodies
Peptides
Receptors, Transforming Growth Factor beta
Thymidine
Transforming Growth Factor beta
Transforming Growth Factor beta1