Antisense inhibition of cyclin D1 in human head and neck squamous cell carcinoma.
OBJECTIVE
To study the role of cyclin D1 in regulating the biological behavior of head and neck cancer.


METHODS
Squamous cell carcinoma of the head and neck (SCCHN) cells were stably transfected with an antisense cyclin D1 using lipofectin-mediated transfection. In vitro growth assays, cell cycle analyses, cytotoxicity assays, and in vivo tumorigenicity assays were performed.


METHODS
Human SCCHN cell lines TU138, TU167, TU177, TU182, MDA183, and MDA1386 and athymic nude mice were used for this study.


RESULTS
The antisense cyclin D1 transfected cells revealed decreased growth rates in vitro and decreased tumorigenicity in athymic nude mice. Furthermore, antisense cyclin D1 transfection enhanced the chemosensitivity against cisplatin.


CONCLUSIONS
These studies provided evidence that overexpression of cyclin D1 may play an important role in growth rates and biological behavior of human head and neck cancer. Additionally, expression of cyclin D1 may make human head and neck cancer cells resistant to platinum-based chemotherapeutic approaches. The ability to suppress the malignant phenotype by down-regulating cyclin D1 expression may provide a new gene therapy approach for patients with head and neck cancer.
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
T
T
Nakashima
G L
GL
Clayman
D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D016375:Antisense Elements (Genetics) / Q000235:genetics*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004587:Electrophoresis, Agar Gel / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000187:drug effects / Q000235:genetics; D018816:Genes, cdc / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D014162:Transfection / Q000235:genetics
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D016375:Antisense Elements (Genetics); D019938:Cyclin D1; D002945:Cisplatin