Overexpression of cyclin D1 correlates with sensitivity to cisplatin in squamous cell carcinoma cell lines of the head and neck.
OBJECTIVE
Treatment strategies for squamous cell carcinoma of the head and neck (SCCHN) are based on the TNM classification. Biological markers that can predict the response to therapy have so far not been introduced. The objective of this study was to investigate cyclin D1 deregulation relative to sensitivity to cisplatin.


METHODS
This was a laboratory study of 23 established University of Michigan SCC cell lines. Chemosensitivity was assessed by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cyclin D1 amplification status was evaluated by real-time polymerase chain reaction (PCR; data were verified by differential and conventional PCR) using a chromosome 18q microsatellite marker probe (D18S70) as an internal control. Cyclin D1 protein expression was tested using Western blotting.


RESULTS
Cyclin D1 amplification was seen in 9/23 (39%) and cyclin D1 overexpression in 12/19 (63%) of the cell lines. As expected, all cell lines showing amplification also showed overexpression of cyclin D1 (p=0.004; Fisher's exact test). The mean cisplatin concentration inhibiting growth of 50% of the cells (ID50) was 9.8 microM in all cell lines (range 2.7-36.7 microM). Five of nine cell lines showing cyclin D1 amplification were highly sensitive to cisplatin (ID50 3-4.8 microM) and the remaining four revealed intermediate sensitivity. Five cell lines that strongly overexpressed cyclin D1 protein responded better to cisplatin than cell lines that showed any other expression (ID50 5.1 vs 11.2 microM; p=0.025; Student's t-test).


CONCLUSIONS
This in vitro study suggests that overexpression of cyclin D1 is associated with a good response to cisplatin in SCC cell lines. Our results support the hypothesis that overexpression of cyclin D1 is one of the molecular factors that can be used to predict sensitivity to chemotherapy, thus enabling individualization of treatment of head and neck cancer.
University of Michigan Ann Arbor, MI, USA.
Jan
J
Akervall
David M
DM
Kurnit
Meredith
M
Adams
Shaobo
S
Zhu
Susan G
SG
Fisher
Carol R
CR
Bradford
Thomas E
TE
Carey
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D015342:DNA Probes / Q000235:genetics; D018572:Disease-Free Survival; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D019940:Genes, bcl-1 / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015342:DNA Probes; D002945:Cisplatin