Inhibition of tumourigenicity of small cell lung cancer cells by suppressing Id3 expression.
Id3 is over-expressed in small cell lung cancer (SCLC). To test whether the tumourigenicity of SCLC cells can be inhibited by suppressing Id3 expression, we transfected siRNA into SCLC cell line GLC-19 and established two sublines (G-Id3-1 and G-Id3-7) which expressed only 30% of the level of Id3 measured in control transfectants. Suppression of Id3 expression in both G-Id3-1 and G-Id3-7 cells produced significant reductions in proliferation rates and in numbers of colonies formed in soft agar assay. When G-Id3-1, G-Id3-7 and the control transfectants were inoculated subcutaneously into 3 groups (8 each) of nude mice, respectively, all (100%) inoculated animals produced tumours. Although there was no difference in tumour incidents amongst the 3 groups, significant reductions were observed in both size and weight of tumours produced by either G-Id3-1 or G-Id3-7 cells. While the final average volume of tumours produced in control group was 1012.1+/-394 mm(3), it was significantly reduced (p<0.001, p<0.01) by 2.1- and 2.9-fold to 475.7+/-167 mm(3) and 354.3+/-218 mm(3) in groups inoculated with G-Id3-1 and G-Id3-7 cells, respectively. Similar differences were also observed in average weight of tumours. Upon induction of apoptosis by cytotoxin camptothecin, the percentages of apoptotic cells in G-Id3-1 and G-Id3-7 were, respectively >2.4-fold higher than that in control. The results in this study suggest that highly expressed Id3 in SCLC cells may be an important therapeutic target for tumour suppression.
Kamalian
Laleh
L
Molecular Pathology Laboratory, School of Cancer Studies, University of Liverpool, 6th Floor, Duncan Building, Daulby Street, Liverpool, L69 3GA, UK.
Forootan
Shiva S
SS
Bao
Zheng Z
ZZ
Zhang
Yu
Y
Gosney
John R
JR
Foster
Christopher S
CS
Ke
Youqiang
Y
D000818:Animals; D001483:Base Sequence; D002166:Camptothecin / Q000494:pharmacology; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D014162:Transfection
D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C075640:ID3 protein, human; D002166:Camptothecin