Extracellular matrix-induced changes in expression of cell cycle-related proteins and proteasome components in endometrial adenocarcinoma cells.
OBJECTIVE
Extracellular matrix (ECM) components regulate growth and differentiation of epithelial cells, and impaired cell-ECM interaction may lead to increased cell proliferation and tumorigenesis. Whereas ECM has been shown to alter cellular morphology and reduce proliferation of HEC-1B endometrial adenocarcinoma cells, little is known about the underlying changes in gene expression. The purpose of this study was to investigate these changes.


METHODS
We studied by cDNA array the effects of ECM components, as present in Matrigel basement membrane cell culture matrix, on gene expression in HEC-1B endometrial adenocarcinoma cells in respect of the same cells cultured on conventional plastic surface. Some of the changes were confirmed by protein analyses.


RESULTS
As expected, several growth-promoting genes were downregulated, while many genes associated with growth restriction were upregulated in Matrigel-grown carcinoma cells. Also, the expression of many 20S proteasome components was downregulated. The observed changes point to a less malignant phenotype of Matrigel-grown tumor cells, supported by reduced growth characteristics and morphology.


CONCLUSIONS
The study provides further insight into the mechanisms whereby ECM components may participate in the regulation of cell growth--by reducing expression of growth-promoting genes and increasing expression of the genes associated with growth restriction.
Department of Clinical Chemistry, Helsinki University Central Hospital, Biomedicum Helsinki, PO Box 700, 00029 HUS, Finland. hannu.k.koistinen@helsinki.fi
Hannu
H
Koistinen
Markku
M
Seppälä
Sakari
S
Knuutila
Riitta
R
Koistinen
D000230:Adenocarcinoma / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D003094:Collagen; D004338:Drug Combinations; D016889:Endometrial Neoplasms / Q000378:metabolism*; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011509:Proteoglycans; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D046988:Proteasome Endopeptidase Complex