Clinical & Experimental Metastasis

, Volume 12, Issue 3, pp 181–194 | Cite as

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
Article

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 linesin vitro andin 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 determinedin vitro using Matrigel, a reconstituted basement membrane extract. Lineage-specific differences were observed with respect to low constitutive invasiveness and invasive changes after infection withras, despite similarras-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.

Keywords

basement membrane human breast cancer invasion oncogene uvomorulin vimentin 

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Copyright information

© Rapid Communications of Oxford Ltd 1994

Authors and Affiliations

  • Erik W. Thompson
    • 1
    • 2
    • 5
  • Jeffrey Torri
    • 1
  • Marybeth Sabol
    • 1
  • Connie L. Sommers
    • 1
    • 2
  • Stephen Byers
    • 2
  • Eva M. Valverius
    • 1
  • George R. Martin
    • 3
  • Marc E. Lippman
    • 1
  • Martha R. Stampfer
    • 4
  • Robert B. Dickson
    • 1
    • 2
  1. 1.Vincent T. Lombardi Cancer Research CenterUSA
  2. 2.Department of Cell BiologyGeorgetown University Medical CenterNW Washington, DCUSA
  3. 3.Laboratory of Developmental BiologyNational Institute of Dental Research
  4. 4.Lawrence Berkeley LaboratoryUSA
  5. 5.Department of PathologyUniversity HospitalUppsalaSweden

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