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Overexpression of cyclin D1 correlates with sensitivity to cisplatin in squamous cell carcinoma cell lines of the head and neck

Åkervall, Jan LU ; Kurnit, DM; Adams, M; Zhu, SB; Fisher, SG; Bradford, CR and Carey, TE (2004) In Acta Oto-Laryngologica 124(7). p.851-857
Abstract
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. Material and 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... (More)
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. Material and 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 muM in all cell lines (range 2.7-36.7 muM). Five of nine cell lines showing cyclin D1 amplification were highly sensitive to cisplatin (ID50 3-4.8 muM) 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 muM; 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
head and neck, gene expression, chemosensitivity, cyclin D1, cell carcinoma, squamous
in
Acta Oto-Laryngologica
volume
124
issue
7
pages
851 - 857
publisher
Taylor & Francis
external identifiers
  • wos:000223997900016
  • pmid:15484403
  • scopus:4644281290
ISSN
1651-2251
DOI
10.1080/00016480410017323
language
English
LU publication?
yes
id
89d46e24-a813-4ac8-9ffc-667232482d4a (old id 267659)
date added to LUP
2007-08-29 09:26:28
date last changed
2017-05-07 04:23:03
@article{89d46e24-a813-4ac8-9ffc-667232482d4a,
  abstract     = {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. Material and 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 muM in all cell lines (range 2.7-36.7 muM). Five of nine cell lines showing cyclin D1 amplification were highly sensitive to cisplatin (ID50 3-4.8 muM) 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 muM; 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.},
  author       = {Åkervall, Jan and Kurnit, DM and Adams, M and Zhu, SB and Fisher, SG and Bradford, CR and Carey, TE},
  issn         = {1651-2251},
  keyword      = {head and neck,gene expression,chemosensitivity,cyclin D1,cell carcinoma,squamous},
  language     = {eng},
  number       = {7},
  pages        = {851--857},
  publisher    = {Taylor & Francis},
  series       = {Acta Oto-Laryngologica},
  title        = {Overexpression of cyclin D1 correlates with sensitivity to cisplatin in squamous cell carcinoma cell lines of the head and neck},
  url          = {http://dx.doi.org/10.1080/00016480410017323},
  volume       = {124},
  year         = {2004},
}