Mitogenic Activity of Growth Factors in the Human Endometrial Adenocarcinoma Cell Lines HEC-1-A and KLE

Endometrial adenocarcinoma is the most common gynecologic malignancy occurring in the United States. Evidence is accumulating that links peptide growth factors with malignant proliferation. Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) are known mitogens for endometrial adenocarcinoma in vitro. However, the biological activity of other growth factors in this malignancy is unclear. This study was undertaken to determine the influence of growth factors on the mitogenic activity of the human endometrial adenocarcinoma cell lines HEC-1-A and KLE. Incubation with EGF, IGF-I, insulin-like growth factor II (IGF-II), or insulin stimulated a time-dependent mitogenic response in both cell lines, with the peak response occurring at 24 hr for HEC-1-A and 48 hr for KLE. After two doubling intervals, the number of HEC-1-A cells was increased 3.5-fold by EGF (100 ng/ml), 2.7-fold by IGF-I (100 ng/ml), 2.3-fold by IGF-II (100 ng/ml), and 2.2-fold by insulin (1000 ng/ml) when compared to untreated controls (P P < 0.05). Similar results were obtained when DNA content was measured. PDGF failed to stimulate any mitogenic response in either cell line at all concentrations tested (0.1-100 ng/ml). These findings suggest that EGF, IGF-I, IGF-II, and insulin may play a regulatory role in the proliferation of endometrial adenocarcinoma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30772/1/0000423.pd

Protein Kinase C-Dependent and -Independent Pathways Mediate Epidermal Growth Factor (EGF) Effects in Human Endometrial Adenocarcinoma Cell Line KLE

The role of EGF in the proliferation of the poorly differentiated endometrial adenocarcinoma cell line (KLE) was examined. EGF (10 ng/ml) and the tumor promoter, protein kinase C agonist, phorbol 12-myristate 13-acetate (PMA) were potent stimulators (P 3H]thymidine incorporation into DNA. Staurosporine, a protein kinase C inhibitor, partially blocked the EGF effects on [3H]thymidine incorporation. Similarly, downregulation of protein kinase C also failed to completely abolish EGF effect on DNA synthesis and cell division. These results suggest that in the KLE cell line EGF stimulation of cell growth is exerted through both protein kinase C-dependent and -independent pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31609/3/0000538.pd