The induction of spermidine/spermine N1-acetyltransferase (SSAT) is a common event in the response of human primary non-small cell lung carcinomas to exposure to the new antitumor polyamine analogue N1,N11-bis(ethyl)norspermine.
Several new polyamine analogues have been developed for the treatment of human solid tumors. The phenotype-specific activity of some of these analogues has been associated with the superinduction of the rate-limiting enzyme in polyamine catabolism spermidine/spermine N1-acetyltransferase (SSAT). Using immunohistochemistry, we found a majority (64%) of human primary lung cancer explants to exhibit high expression of SSAT after treatment with 10 microM N1,N11-bis(ethyl)norspermine, an agent currently undergoing Phase II clinical trials against several important human solid tumors. The staining of SSAT was found specifically in the tumor tissue and not in the neighboring normal lung tissue. These results demonstrate the ability to detect induction of SSAT in clinical specimens and suggest the potential of this test as a prognostic indicator of drug response.
Gabrielson
E W
EW
Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA.
Pegg
A E
AE
Casero
R A
RA
D000123:Acetyltransferases / Q000096:biosynthesis* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D008297:Male; D017063:Outcome Assessment, Health Care / Q000379:methods; D010641:Phenotype; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology; D013096:Spermine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D000970:Antineoplastic Agents; D015415:Biomarkers; D011073:Polyamines; D013096:Spermine; D000099228:Diamine N-Acetyltransferase; C059685:N(1),N(11)-diethylnorspermine