Proliferation-associated increase in sensitivity of mammary epithelial cells to inositol-1,4,5-trisphosphate.
Injection of D-myo-inositol-1,4,5-trisphosphate (IP3) was found to induce a transient increase of intracellular Ca2+ concentration in cancerous mammary cells (MMT060562) and in normal mammary cells treated with epidermal growth factor. Responses to injection of either D-myo-inositol-1,4-bisphosphate (IP2) or D-myo-inositol-1,3,4,5-tetrakisphosphate (IP4) were small or absent. Furthermore, normal mammary cells cultivated with low-protein serum replacement alone or in the presence of differentiation-inducing hormones (insulin + cortisol + prolactin) were less sensitive to IP3. Thapsigargin induced a transient increase of Ca2+ due to the release of Ca2+ from an intracellular pool. There was no difference in the peak heights of the thapsigargin-induced Ca2+ increase when mammary cells were cultivated in the presence or absence of epidermal growth factor or insulin + cortisol + prolactin. These findings suggest that the releasable intracellular Ca2+ pool remained unchanged whereas sensitivity to IP3 increases during the proliferation stage. Mechanical stimulus of a mammary cell induces an increase of intracellular Ca2+ in the stimulated cell. A certain stimulating factor is released from the mechanically stimulated cell into the extracellular space, and it induces an increase of Ca2+ in surrounding cells. In contrast, the IP3-induced Ca2+ increase in both cancerous and epidermal growth factor-treated normal mammary cells did not spread to adjacent cells. Therefore, increase of Ca2+ is not sufficient to account for the release of stimulating substances from mammary cells in the mechanically-induced spreading response.
Enomoto
K
K
Department of Physiology, Shimane Medical University, Izumo, Japan.
Furuya
K
K
Yamagishi
S
S
Maeno
T
T
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D004351:Drug Resistance; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005260:Female; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000166:cytology*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D012433:Ryanodine / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014407:Tumor Cells, Cultured
D007295:Inositol Phosphates; D013729:Terpenes; C081655:inositol-1,3,4,5-tetrakisphosphate; D012433:Ryanodine; D002110:Caffeine; C044259:inositol 1,4-bis(phosphate); D004815:Epidermal Growth Factor; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium