Back to Search
Start Over
Characterisation of molecular events following cisplatin treatment of two curable ovarian cancer models: contrasting role for p53 induction and apoptosis in vivo.
- Source :
-
British journal of cancer [Br J Cancer] 2004 Oct 18; Vol. 91 (8), pp. 1614-23. - Publication Year :
- 2004
-
Abstract
- The detailed molecular basis and determinants of in vivo tumour sensitivity to conventional anticancer agents remain unclear. We examined the cellular and molecular consequences of cisplatin treatment using two ovarian tumour xenograft models that had not been previously adapted to culture in vitro. Both xenografts were curable with clinically relevant multiple doses of cisplatin. Following a single dose of cisplatin (6 mg kg(-1) i.p.) growth delays of 25 and 75 days were obtained for pxn100 and pxn65, respectively. This difference in response was not due to differences in DNA damage. Pxn100 tumours had a functional p53 response and a wild-type p53 sequence, whereas pxn65 harboured a mutant p53 and lacked a functional p53 response. Microarray analysis revealed the induction of p53-regulated genes and regulators of checkpoint control and apoptosis in pxn100 tumours following cisplatin-treatment. By contrast, there was no p53-dependent response and only limited changes in gene expression were detected in the pxn65 tumours. TUNEL analysis demonstrated high levels of apoptosis in the pxn100 tumours following cisplatin treatment, but there was no detectable apoptosis in the pxn65 tumours. Our observations show that a marked in vivo response to cisplatin can occur via p53-dependent apoptosis or independently of p53 status in human ovarian xenografts.
- Subjects :
- Adenocarcinoma drug therapy
Adenocarcinoma metabolism
Adenocarcinoma pathology
Animals
Cell Cycle
DNA Adducts
DNA Damage
Disease Models, Animal
Endodermal Sinus Tumor drug therapy
Endodermal Sinus Tumor metabolism
Endodermal Sinus Tumor pathology
Female
Gene Expression Profiling
Humans
In Situ Nick-End Labeling
Mice
Mice, Nude
Mutation
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms pathology
Transplantation, Heterologous
Tumor Suppressor Protein p53 genetics
Antineoplastic Agents therapeutic use
Apoptosis drug effects
Cisplatin therapeutic use
Ovarian Neoplasms drug therapy
Ovarian Neoplasms metabolism
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0007-0920
- Volume :
- 91
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 15452549
- Full Text :
- https://doi.org/10.1038/sj.bjc.6602167