S-adenosylmethionine decarboxylase overexpression reduces invasiveness andtumorigenicity in nude mice of MCF-7 breast cancer cells

To elucidate the role of S-adenosylmethionine decarboxylase (SAMDC) in brea st cancer biology, we have generated SAMDC overexpressing MCF-7 breast canc er cells. SAMDC overexpression did not alter in a major way growth properti es of MCF-7 cells in soft agar, either under basal conditions or in respons e to estrogen and antiestrogen administration. SAMDC-MCF-7 cells, on the ot her hand, exhibited a markedly reduced invasive ability in matrigel (p=0.01 3). Furthermore, they were less tumorigenic in nude mice. The odds for cont rol clones to form tumors were 3.13 (C.1.1.2-8.2, p=0.0184) higher than tho se for SAMDC clones. The odds ratio were identical in the absence and in th e presence of estradiol. In addition, the growth rate of established tumors was slower for SAMDC than for control clones. Overall, our results are con sistent with the notion that these phenotypic changes induced by SAMDC over expression are primarily mediated by suppression of cellular putrescine (an d,possibly,spermidine) levels.