ArticleBritish journal of cancer2010
Trastuzumab induced in vivo tissue remodelling associated in vitro with inhibition of the active forms of AKT and PTEN and RhoB induction in an ovarian carcinoma model.
Article in British journal of cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 13 citations in OpenAlex.
- Review
- Regulation of RhoB Gene Expression during Tumorigenesis and Aging Process and Its Potential Applications in These Processes.Cancers · 2019Review
- Negative Regulation of PTEN by MicroRNA-221 and Its Association with Drug Resistance and Cellular Senescence in Lung Cancer Cells.BioMed research international · 2018Article
- RhoB loss induces Rac1-dependent mesenchymal cell invasion in lung cells through PP2A inhibition.Oncogene · 2016Article
- Study of drug function based on similarity of pathway fingerprint.Protein & cell · 2012Article
- Primary trastuzumab resistance: new tricks for an old drug.Annals of the New York Academy of Sciences · 2010Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe incidence of ovarian cancer has been increasing worldwide and it is currently the leading cause of death from gynaecological malignancy. Unlike breast cancer, the prognostic role of the human epidermal growth factor receptor-2 (HER-2) in ovarian carcinoma remains controversial.
methodsThe aim of this preclinical study was to further characterise the biological, molecular and cellular effects of trastuzumab (Herceptin) using NIH-OVCAR-3 and derived cell lines both in vitro and in vivo.
resultsIn vitro assessments have shown that trastuzumab treatment inhibited total and phosphorylated HER-2. This was associated with inhibition of the phosphorylated form of phosphatase and tensin homologue (PTEN), mitogen-activated protein kinase and AKT, and the total level of p27(kip). Inhibition of PTEN is associated with phosphorylated MEK1/2 upregulation, suggesting a specific inhibition of the protein phosphatase function of PTEN. Moreover, trastuzumab induced the upregulation of RhoB. These molecular modifications promote inhibition of cell migration and potentially restoration of tumour cell contact inhibition. RhoB induction in NIH-OVCAR-3 control cell lines mimics the molecular and cellular trastuzumab long-time exposition effects. RhoB inhibition in NIH-OVCAR-3 long-time exposed to trastuzumab cell line reverses the cellular and molecular effects observed in this model. In vivo examinations have shown that these changes are also associated with the restoration of structural, morphological and normal functions of the peritoneum of an ovarian carcinoma mouse model.
conclusionThese results provide an indication of the mechanisms underlying the anti-tumour activity of trastuzumab that strongly implicate RhoB in an ovarian carcinoma model that does not show HER-2 amplification or overexpression. These findings highlight that trastuzumab effects involve a possible cross-talk between RhoB and PTEN in the early stages of tumour re-growth in a model of micrometastatic ovarian cancer.
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