ANTISENSE GALECTIN-3 ALTERS THYMIDINE INCORPORATION IN HUMAN MDA-MB435 BREAST-CANCER CELLS

Galectin-3 is a 30-kDa galactose-binding protein member of the galecti n family. Galectin-3 is involved in multiple intracellular and extrace llular biological functions, e.g. interactions with laminin and with n ucleic acids. This latter property is consistent with the presence of 3. serum-response factor-like domain at the amino-terminal part of the protein. Galectin-3 expression is upregulated during serum-mediated i nduction of proliferation. In order to examine the role of galectin-3 in breast cancer cell proliferation, we examined in this study the inf luence of antisense galectin-3 complementary DNA stable transfection o n the in vitro thymidine incorporation of human breast cancer MDA-MB43 5 cells. Two stable transfectants, clones 5.24 and 5.29, were selected based both on the presence of a complete CMV promoter-antisense galec tin-3 cDNA cassette as assayed by polymerase chain reaction, and on ef ficient down-regulation of galectin-3 protein expression as determined by Western blotting. Thymidine incorporation experiments showed that both clones were characterized by significantly decreased values of DN A incorporation compared to wild-type transfectants (55 to 68%, and 71 to 82% of the control clone values). Our data demonstrate for the fir st time that galectin-3 decreases thymidine incorporation in breast ca ncer cells. The mechanism underlying this property of galectin-3 and i ts importance during breast cancer development remain to be elucidated .