Manni A, Fischer S, Franks M, Washington S, De Arment R, Griffith J, Demers L, Verderame M, Leiby B, Mauger D
Division of Endocrinology, H044 Hershey Medical Center, 500 University Drive, Hershey, PA 17033-0850, USA.
Int J Oncol. 2001 Aug;19(2):317-23. doi: 10.3892/ijo.19.2.317.
To elucidate the role of S-adenosylmethionine decarboxylase (SAMDC) in breast cancer biology, we have generated SAMDC overexpressing MCF-7 breast cancer cells. SAMDC overexpression did not alter in a major way growth properties of MCF-7 cells in soft agar, either under basal conditions or in response to estrogen and antiestrogen administration. SAMDC-MCF-7 cells, on the other hand, exhibited a markedly reduced invasive ability in matrigel (p=0.013). Furthermore, they were less tumorigenic in nude mice. The odds for control clones to form tumors were 3.13 (C.1.1.2-8.2, p=0.0184) higher than those for SAMDC clones. The odds ratio were identical in the absence and in the presence of estradiol. In addition, the growth rate of established tumors was slower for SAMDC than for control clones. Overall, our results are consistent with the notion that these phenotypic changes induced by SAMDC overexpression are primarily mediated by suppression of cellular putrescine (and, possibly, spermidine) levels.
为阐明S-腺苷甲硫氨酸脱羧酶(SAMDC)在乳腺癌生物学中的作用,我们构建了过表达SAMDC的MCF-7乳腺癌细胞。无论是在基础条件下,还是在给予雌激素和抗雌激素时,SAMDC的过表达都没有显著改变MCF-7细胞在软琼脂中的生长特性。另一方面,SAMDC-MCF-7细胞在基质胶中的侵袭能力明显降低(p = 0.013)。此外,它们在裸鼠中的致瘤性较低。对照克隆形成肿瘤的几率比SAMDC克隆高3.13(置信区间1.2 - 8.2,p = 0.0184)。在不存在和存在雌二醇的情况下,优势比相同。此外,已形成肿瘤的生长速度,SAMDC克隆比对照克隆慢。总体而言,我们的结果与以下观点一致,即SAMDC过表达诱导的这些表型变化主要是由细胞腐胺(可能还有亚精胺)水平的抑制介导的。