Croxtall J D, Waheed S, Choudhury Q, Anand R, Flower R J
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College, St. Batholomew's Hospital, London, UK.
Int J Cancer. 1993 Apr 22;54(1):153-8. doi: 10.1002/ijc.2910540124.
Lipocortin-1 mediates growth inhibition of glucocorticoids in A549 cells by suppressing the release of PGE2 necessary for their proliferation. We now show that 2 peptide fragments derived from the N-terminal portion of lipocortin-1 corresponding to amino-acids 13-25 and 21-33 also inhibited A549 cell growth and suppressed release of PGE2, whereas peptides 1-12 and 13-25 (Phe21; in which the tyrosine at position 21 was replaced by a phenylalanine residue) were inactive. Similarly, peptide 21-33 (Phe21) and a scrambled sequence of 13-25 failed to inhibit cell growth. Moreover, the EGF-induced stimulation of cell proliferation and PGE2 release in these cells was blocked by peptides 13-25 and 21-33, and also by peptides 1-12, 13-25 (Phe21) and 21-33 (Phe21), but not by a scrambled sequence of peptide 13-25.
脂皮质素-1通过抑制A549细胞增殖所需的PGE2释放来介导糖皮质激素的生长抑制作用。我们现在表明，源自脂皮质素-1 N端部分、对应于氨基酸13 - 25和21 - 33的2个肽片段也能抑制A549细胞生长并抑制PGE2释放，而肽1 - 12和13 - 25（Phe21，其中第21位的酪氨酸被苯丙氨酸残基取代）无活性。同样，肽21 - 33（Phe21）和13 - 25的乱序序列未能抑制细胞生长。此外，这些细胞中表皮生长因子诱导的细胞增殖和PGE2释放受到肽13 - 25和21 - 33的阻断，也受到肽1 - 12、13 - 25（Phe21）和21 - 33（Phe21）的阻断，但不受肽13 - 25乱序序列的阻断。
