Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72755
Title:
Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo.
Authors:
Wärnberg, Fredrik; White, Daniel J; Anderson, Elizabeth; Knox, W Fiona; Clarke, Robert B; Morris, Julie; Bundred, Nigel J
Abstract:
INTRODUCTION: The ras pathway is essential for cell growth and proliferation. The effects of R115777, a farnesyl transferase inhibitor, were investigated in cancer cell lines expressing varying levels of growth factor receptors and with differing ras status. Effects on tumour xenografts and human ductal carcinoma in situ (DCIS) of the breast in a xenograft mouse model were also tested. METHOD: In vitro, the concentrations required to reduce cell numbers by 50% (50% inhibitory concentration) were established (MDA-MB231, MCF-7, MCF-7/HER2-18, BT-474, SK-BR3 and SKOV3). Human DCIS was implanted in nude mice or, in separate experiments, cultured cells were injected (MDA-MB231, MCF-7/HER2-18, SKOV3) and allowed to form tumours. Proliferation and apoptosis were determined by immunohistochemistry in xenografts and cell tumours. RESULTS: The 50% inhibitory concentrations varied a hundred-fold, from 39 nmol/l (+/- 26 nmol/l) for SKBR3 to 5.9 micromol/l(+/- 0.8 micromol/l) for MDA-MB231. In MCF-7/HER2-18 and SKOV3 cells the levels of tumour growth inhibition were approximately 85% and 40%, respectively. There was a significant decrease in the cell turnover index (CTI; proliferation/apoptosis). In MDA-MB 231 with activated k-ras no inhibition was observed. In treated DCIS xenografts proliferation decreased and apoptosis increased. The CTI ratio between the start and 1 and 2 weeks of treatment were 1.99 and 1.50, respectively, for controls and 0.85 (P = 0.005) and 0.75 (P = 0.08) for treated xenografts. CONCLUSION : Treatment with the farnesyl transferase inhibitor reduced cell growth in vitro and cell tumour growth in vivo. In DCIS treatment resulted in a reduced CTI. R115777 is a promising treatment for breast cancer but the relation between effect and growth factor receptor and ras status has to be established.
Affiliation:
Breast Biology Group, Christie Hospital NHS Trust, Manchester, UK. fredrik.warnberg@akademiska.se
Citation:
Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo. 2006, 8 (2):R21 Breast Cancer Res.
Journal:
Breast Cancer Research
Issue Date:
2006
URI:
http://hdl.handle.net/10541/72755
DOI:
10.1186/bcr1395
PubMed ID:
16611371
Type:
Article
Language:
en
ISSN:
1465-542X
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWärnberg, Fredrik-
dc.contributor.authorWhite, Daniel J-
dc.contributor.authorAnderson, Elizabeth-
dc.contributor.authorKnox, W Fiona-
dc.contributor.authorClarke, Robert B-
dc.contributor.authorMorris, Julie-
dc.contributor.authorBundred, Nigel J-
dc.date.accessioned2009-07-07T11:45:13Z-
dc.date.available2009-07-07T11:45:13Z-
dc.date.issued2006-
dc.identifier.citationEffect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo. 2006, 8 (2):R21 Breast Cancer Res.en
dc.identifier.issn1465-542X-
dc.identifier.pmid16611371-
dc.identifier.doi10.1186/bcr1395-
dc.identifier.urihttp://hdl.handle.net/10541/72755-
dc.description.abstractINTRODUCTION: The ras pathway is essential for cell growth and proliferation. The effects of R115777, a farnesyl transferase inhibitor, were investigated in cancer cell lines expressing varying levels of growth factor receptors and with differing ras status. Effects on tumour xenografts and human ductal carcinoma in situ (DCIS) of the breast in a xenograft mouse model were also tested. METHOD: In vitro, the concentrations required to reduce cell numbers by 50% (50% inhibitory concentration) were established (MDA-MB231, MCF-7, MCF-7/HER2-18, BT-474, SK-BR3 and SKOV3). Human DCIS was implanted in nude mice or, in separate experiments, cultured cells were injected (MDA-MB231, MCF-7/HER2-18, SKOV3) and allowed to form tumours. Proliferation and apoptosis were determined by immunohistochemistry in xenografts and cell tumours. RESULTS: The 50% inhibitory concentrations varied a hundred-fold, from 39 nmol/l (+/- 26 nmol/l) for SKBR3 to 5.9 micromol/l(+/- 0.8 micromol/l) for MDA-MB231. In MCF-7/HER2-18 and SKOV3 cells the levels of tumour growth inhibition were approximately 85% and 40%, respectively. There was a significant decrease in the cell turnover index (CTI; proliferation/apoptosis). In MDA-MB 231 with activated k-ras no inhibition was observed. In treated DCIS xenografts proliferation decreased and apoptosis increased. The CTI ratio between the start and 1 and 2 weeks of treatment were 1.99 and 1.50, respectively, for controls and 0.85 (P = 0.005) and 0.75 (P = 0.08) for treated xenografts. CONCLUSION : Treatment with the farnesyl transferase inhibitor reduced cell growth in vitro and cell tumour growth in vivo. In DCIS treatment resulted in a reduced CTI. R115777 is a promising treatment for breast cancer but the relation between effect and growth factor receptor and ras status has to be established.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectOvarian Canceren
dc.subjectCell Line Tumouren
dc.subject.meshAnimals-
dc.subject.meshBreast Neoplasms-
dc.subject.meshCalcinosis-
dc.subject.meshCarcinoma, Intraductal, Noninfiltrating-
dc.subject.meshCell Division-
dc.subject.meshCell Line, Tumor-
dc.subject.meshFarnesyltranstransferase-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshMammography-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshMice, Nude-
dc.subject.meshOvarian Neoplasms-
dc.subject.meshQuinolones-
dc.subject.meshTransplantation, Heterologous-
dc.titleEffect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo.en
dc.typeArticleen
dc.contributor.departmentBreast Biology Group, Christie Hospital NHS Trust, Manchester, UK. fredrik.warnberg@akademiska.seen
dc.identifier.journalBreast Cancer Researchen

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