Glycodelin reduces breast cancer xenograft growth in vivo.
Malignant growth is characterized by loss of cell differentiation, uncontrolled proliferation and resistance to apoptosis. Many tumor suppressor genes that protect cells against malignant transformation regulate cell differentiation. Here, we show for the first time that glycodelin, a differentiation-related protein, reduces breast cancer tumor growth in vivo. We found that glycodelin cDNA-transfected MCF-7 breast cancer cells showed a differentiated phenotype and produced smaller tumors in mouse mammary fat pads compared with control-transfected cells. Glycodelin-induced differentiation was associated with reduced expression of oncogenes and increased expression of tumor suppressor genes. Our results suggest that glycodelin acts as a tumor suppressor in breast cancer. This may explain its reported association with a more favorable prognosis in some cancers.
Hautala
Laura C
LC
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Koistinen
Riitta
R
Seppälä
Markku
M
Bützow
Ralf
R
Stenman
Ulf-Håkan
UH
Laakkonen
Pirjo
P
Koistinen
Hannu
H
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D020869:Gene Expression Profiling; D000071816:Glycodelin; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D011257:Pregnancy Proteins / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000071816:Glycodelin; D006023:Glycoproteins; C045246:PAEP protein, human; D011257:Pregnancy Proteins