Oncogene-induced basement membrane invasiveness in human mammary epithelial cells

Erik W. Thompson, Jeffrey Torri, Marybeth Sabol, Connie L. Sommers, Stephen Byers, Eva M. Valverius, George R. Martin, Marc E Lippman, Martha R. Stampfer, Robert B. Dickson

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)181-194
Number of pages14
JournalClinical & Experimental Metastasis
Volume12
Issue number3
DOIs
StatePublished - May 1 1994
Externally publishedYes

Fingerprint

Cadherins
Oncogenes
Basement Membrane
Breast
Epithelial Cells
Vimentin
Exanthema
Cell Membrane
Breast Neoplasms
Intermediate Filament Proteins
Cell Line
Epithelial-Mesenchymal Transition
Benzo(a)pyrene
Nuclear Envelope
Matrix Metalloproteinase 9
Laminin
Infection
Phenotype
Proteins
In Vitro Techniques

Keywords

  • basement membrane
  • human breast cancer
  • invasion
  • oncogene
  • uvomorulin
  • vimentin

ASJC Scopus subject areas

  • Cancer Research

Cite this

Thompson, E. W., Torri, J., Sabol, M., Sommers, C. L., Byers, S., Valverius, E. M., ... Dickson, R. B. (1994). Oncogene-induced basement membrane invasiveness in human mammary epithelial cells. Clinical & Experimental Metastasis, 12(3), 181-194. https://doi.org/10.1007/BF01753886

Oncogene-induced basement membrane invasiveness in human mammary epithelial cells. / Thompson, Erik W.; Torri, Jeffrey; Sabol, Marybeth; Sommers, Connie L.; Byers, Stephen; Valverius, Eva M.; Martin, George R.; Lippman, Marc E; Stampfer, Martha R.; Dickson, Robert B.

In: Clinical & Experimental Metastasis, Vol. 12, No. 3, 01.05.1994, p. 181-194.

Research output: Contribution to journalArticle

Thompson, EW, Torri, J, Sabol, M, Sommers, CL, Byers, S, Valverius, EM, Martin, GR, Lippman, ME, Stampfer, MR & Dickson, RB 1994, 'Oncogene-induced basement membrane invasiveness in human mammary epithelial cells', Clinical & Experimental Metastasis, vol. 12, no. 3, pp. 181-194. https://doi.org/10.1007/BF01753886
Thompson EW, Torri J, Sabol M, Sommers CL, Byers S, Valverius EM et al. Oncogene-induced basement membrane invasiveness in human mammary epithelial cells. Clinical & Experimental Metastasis. 1994 May 1;12(3):181-194. https://doi.org/10.1007/BF01753886
Thompson, Erik W. ; Torri, Jeffrey ; Sabol, Marybeth ; Sommers, Connie L. ; Byers, Stephen ; Valverius, Eva M. ; Martin, George R. ; Lippman, Marc E ; Stampfer, Martha R. ; Dickson, Robert B. / Oncogene-induced basement membrane invasiveness in human mammary epithelial cells. In: Clinical & Experimental Metastasis. 1994 ; Vol. 12, No. 3. pp. 181-194.
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