EGF enhances Ca(2+) mobilization and capacitative Ca(2+) entry in mouse mammary epithelial cells.
Effects of epidermal growth factor (EGF) on the intracellular Ca(2+) ([Ca(2+)](i)) responses to nucleotides, Ca(2+) release from thapsigargin-sensitive stores and capacitative Ca(2+) entry were investigated in cultured mouse mammary epithelial cells. EGF treatment induced proliferation of mammary epithelial cells. We checked for mitotic activity by immunocytochemistry with an anti-PCNA (proliferating cell nuclear antigen) antibody, which stains nuclei of the cells in S-phase of cell cycle. EGF treatment apparently increased the number of PCNA-stained cells compared to those treated with differentiating hormones (insulin, prolactin and cortisol) or without any hormone. Application of EGF did not induce any acute [Ca(2+)](i) response. EGF treatment for 1-2 days in culture, however, enhanced [Ca(2+)](i) responses including [Ca(2+)](i) increase by ATP, UTP and other nucelotides, Ca(2+) release from thapsigargin-sensitive stores, as well as capacitative Ca(2+) entry. Genistein, a tyrosine kinase inhibitor, prevented EGF-induced cell proliferation and the [Ca(2+) ](i) responses in a dose-dependent manner. These results indicate that EGF treatment enhances Ca(2+) mobilization and capacitative Ca(2+) entry, well correlated with cellular proliferation in mammary epithelial cells.
Ichikawa
J
J
Kyoto Institute of Technology, Department of Applied Biology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan.
Furuya
K
K
Miyata
S
S
Nakashima
T
T
Kiyohara
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011270:Pregnancy, Animal; D011388:Prolactin / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation; D014544:Uridine Triphosphate / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D007328:Insulin; D018809:Proliferating Cell Nuclear Antigen; D004815:Epidermal Growth Factor; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D011388:Prolactin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D002118:Calcium; D014544:Uridine Triphosphate; D006854:Hydrocortisone