Third place--Resident Research Competition, AAO-2000. Antisense cyclin D1 inhibits growth of head and neck cancer xenografts in nude mice.
OBJECTIVE
Cyclin D1 is a regulatory factor essential in the progression of the cell cycle from G1 through S phase. Amplification and overexpression of cyclin D1 have been observed in many human cancers including head and neck squamous cell carcinoma (HNSCC). We have previously transfected a HNSCC control cell line (CCL23) with an antisense cyclin D1 plasmid and demonstrated inhibition of cell proliferation in vitro. In this study, we examine whether antisense cyclin D1 could inhibit tumor growth in vivo. Methods/measures: The CCL23 and its antisense cyclin D1 transfected clone (CCL23 AS) were injected into the flanks of nude mice. Tumor growth was monitored weekly. After 5 weeks, tumors were removed and studied for tumor size, cyclin D1 expression, cyclin D1-dependent kinase activity, and retinoblastoma (Rb) phosphorylation.


RESULTS
Compared with the control tumors, 11 of 19 antisense tumors were smaller, 7 tumors were of equal size, and 1 tumor was larger. Immunohistochemical analysis with an anti-cyclin D1 antibody demonstrated decreased cyclin D1 expression in CCL23 AS and the smaller antisense tumors. Cyclin D1-dependent kinase activity was reduced in CCL23 AS and the smaller antisense tumors, and this was accompanied by a relative decrease in phosphorylated Rb in these samples.


CONCLUSIONS
Antisense cyclin D1 inhibits growth of HNSCC tumors. Cyclin D1 expression, cyclin D1-dependent kinase activity, and Rb phosphorylation are decreased in these tumors.


CONCLUSIONS
These findings lend support for the potential use of antisense cyclin D1 as gene therapy for HNSCC.
Wang
S J
SJ
Division of Head and Neck Surgery, UCLA School of Medicine, Los Angeles, CA, USA.
Mintz
L E
LE
Natarajan
V
V
Lee
N J
NJ
Srivatsan
E S
ES
Wang
M B
MB
D000818:Animals; D016375:Antisense Elements (Genetics); D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D016375:Antisense Elements (Genetics); D019938:Cyclin D1