Oncogene-induced basement membrane invasiveness in human mammary epithelial cells

Thompson, E.W., Torri, J., Sabol, M., Sommers, C.L., Byers, S., Valverius, E.M., Martin, G.R., Lippman, M.E., Stampfer, M.R., & Dickson, R.B. (1994) Oncogene-induced basement membrane invasiveness in human mammary epithelial cells. Clinical and Experimental Metastasis, 12(3), pp. 181-194.

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Expression of the intermediate filament protein vimentin, and loss of the cellular adhesion protein uvomorulin (E-cadherin) have been associated with increased invasiveness of established human breast cancer cell lines in vitro and in vivo. In the current study, we have further examined these relationships in oncogenically transformed human mammary epithelial cells. A normal human mammary epithelial strain, termed 184, was previously immortalized with benzo[a]pyrene, and two distinct sublines were derived (A1N4 and 184B5). These sublines were infected with retroviral vectors containing a single or two oncogenes of the nuclear, cytoplasmic, and plasma membrane-associated type (v-rasH, v-rasKi, v -mos, SV40T and c -myc). All infectants have been previously shown to exhibit some aspects of phenotypic transformation. In the current study, cellular invasiveness was determined in vitro using Matrigel, a reconstituted basement membrane extract. Lineage-specific differences were observed with respect to low constitutive invasiveness and invasive changes after infection with ras, despite similar ras-induced transformation of each line. Major effects on cellular invasiveness were observed after infection of the cells with two different oncogenes (v-rasH + SV40T and v -rasH + v -mos). In contrast, the effects of single oncogenes were only modest or negligible. All oncogenic infectants demonstrated increased attachment to laminin, but altered secretion of the 72 kDa and 92 kDa gelatinases was not associated with any aspect of malignant progression. Each of the two highly invasive double oncogene transformants were vimentinpositive and uvomorulin-negative, a phenotype indicative of the epithelial-mesenchymal transition (EMT) previously associated with invasiveness of established human breast cancer cell lines. Weakly invasive untransformed mammary epithelial cells in this study were positive for both vimentin and uvomorulin, suggesting that uvomorulin may over-ride the otherwise vimentin-associated invasiveness.

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60 citations in Scopus
58 citations in Web of Science®
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ID Code: 71904
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):48
Export Date: 6 May 2014
Source: Scopus
PubMed ID: 8194193
Additional URLs:
Keywords: basement membrane, human breast cancer, invasion, oncogene, uvomorulin, vimentin
DOI: 10.1007/BF01753886
ISSN: 1573-7276
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 22 May 2014 01:12
Last Modified: 21 Jun 2017 11:01

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