Glycodelin reduces carcinoma-associated gene expression in endometrial adenocarcinoma cells.
OBJECTIVE
Glycodelin is a major secretory glycoprotein of differentiated endometrial epithelium, rarely expressed in proliferative endometrium or endometrial cancer. We aimed to elucidate its role in growth and gene expression of endometrial adenocarcinoma cells, and hypothesized that glycodelin affects cell growth and tumor-associated gene expression.


METHODS
Endometrial adenocarcinoma HEC-1B cells were transfected with glycodelin cDNA in both antisense and sense orientations. Cellular morphology, cell proliferation, and gene expression were compared between native and transfected cells.


RESULTS
Compared with native and antisense-transfected carcinoma cells, sense-transfected, glycodelin-producing carcinoma cells showed reduced proliferation, morphologic changes, and altered expression of cancer-related genes. Notably, anti-apoptotic Bcl-XL and MUC1 genes were down-regulated.


CONCLUSIONS
Reduction by glycodelin transfection of carcinoma cell proliferation and expression of MUC1 and Bcl-XL is significant because these genes are often overexpressed in human cancers--MUC1 is linked to invasive growth and metastases, and both confer resistance to chemotherapy. These results suggest a novel mechanism whereby malignant growth of endometrial adenocarcinoma cells is regulated.
Koistinen
Hannu
H
Department of Clinical Chemistry, Helsinki University Central Hospital, Biomedicum, Helsinki, Finland. Hannu.K.Koistinen@hus.fi
Seppälä
Markku
M
Nagy
Balint
B
Tapper
Johanna
J
Knuutila
Sakari
S
Koistinen
Riitta
R
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000941:Antigens / Q000378:metabolism; D000951:Antigens, Neoplasm; D016375:Antisense Elements (Genetics); D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D000071816:Glycodelin; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D018396:Mucin-1; D009077:Mucins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011257:Pregnancy Proteins / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics; D051020:bcl-X Protein / Q000378:metabolism
D000941:Antigens; D000951:Antigens, Neoplasm; D016375:Antisense Elements (Genetics); D000071816:Glycodelin; D006023:Glycoproteins; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D051020:bcl-X Protein