Elsholtz H P, Shiu R P, Friesen H G
Biochem Cell Biol. 1986 May;64(5):381-6. doi: 10.1139/o86-053.
Mitogenic stimulation of Nb2 lymphoma cells by lactogenic hormones (prolactin, human growth hormone) caused a dramatic early increase in ornithine decarboxylase (ODC) activity that achieved a maximal level by 6-8 h. A marked increase in ODC activity was also generated when cells which had reached a growth plateau were transferred to fresh medium that did not stimulate growth. Furthermore, low concentrations of human growth hormone (20 pg/mL) elicited a proliferative response, but did not cause a detectable early increase in ODC activity. The early peak of ODC activity thus appeared not to be directly involved in mediating lactogen-stimulated growth nor was it required to support the mitogenic response. However, prolonged suppression of ODC activity by DL-alpha-difluoromethylornithine (DFMO) (200 microM) attenuated the growth of Nb2 cells (50-60% inhibition), indicating that normal cell growth was dependent on ODC and polyamine biosynthesis. Under these conditions, putrescine, the enzyme product, or the polyamines spermidine and spermine restored normal cell growth when added at a concentration of 1 microM or greater. Nb2-SP cells, variants which proliferate in the absence of prolactin, were about two times more resistant to the growth suppressive effects of DFMO than prolactin-responsive Nb2 cells.
催乳激素（催乳素、人生长激素）对Nb2淋巴瘤细胞的促有丝分裂刺激导致鸟氨酸脱羧酶（ODC）活性在早期急剧增加，并在6 - 8小时达到最高水平。当达到生长平台期的细胞转移到不刺激生长的新鲜培养基中时，ODC活性也显著增加。此外，低浓度的人生长激素（20 pg/mL）引发了增殖反应，但并未导致ODC活性在早期出现可检测到的增加。因此，ODC活性的早期峰值似乎并未直接参与介导催乳素刺激的生长，也不是支持有丝分裂反应所必需的。然而，用DL-α-二氟甲基鸟氨酸（DFMO）（200 μM）长期抑制ODC活性会减弱Nb2细胞的生长（抑制50 - 60%），这表明正常细胞生长依赖于ODC和多胺生物合成。在这些条件下，当以1 μM或更高浓度添加酶产物腐胺或多胺亚精胺和精胺时，可恢复正常细胞生长。在无催乳素情况下增殖的变体Nb2-SP细胞对DFMO的生长抑制作用的抗性比催乳素反应性Nb2细胞高约两倍。
