S-adenosylmethionine decarboxylase overexpression reduces invasiveness and tumorigenicity in nude mice of MCF-7 breast cancer cells.
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.
Manni
A
A
Division of Endocrinology, H044 Hershey Medical Center, 500 University Drive, Hershey, PA 17033-0850, USA. amanni@psu.edu
Fischer
S
S
Franks
M
M
Washington
S
S
De Arment
R
R
Griffith
J
J
Demers
L
L
Verderame
M
M
Leiby
B
B
Mauger
D
D
D012437:Adenosylmethionine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D000362:Agar; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000517:prevention & control; D002455:Cell Division / Q000187:drug effects; D003094:Collagen; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D004338:Drug Combinations; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D007797:Laminin; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011509:Proteoglycans; D050796:STAT3 Transcription Factor; D012680:Sensitivity and Specificity; D013629:Tamoxifen / Q000494:pharmacology; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D013629:Tamoxifen; C059485:matrigel; D000077267:Fulvestrant; D004958:Estradiol; D004815:Epidermal Growth Factor; D000362:Agar; D003094:Collagen; D012437:Adenosylmethionine Decarboxylase