Invasive phenotype of MCF10A cells overexpressing c‐Ha‐ras and c‐erbB‐2 oncogenes

Daniela Giunciuglio, Martine Culty, Gianfranco Fassina, Luciana Masiello, Antonella Melchiori, Giuseppina Paglialunga, Gloria Arand, Fortunato Ciardiello, Fulvio Basolo, Erik W. Thompson, Adriana Albini

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Abstract

Infection with erbB‐2 (E) of Ha‐roj (H) oncogene‐transfected cells has been previously shown to cooperatively induce anchorage‐independent growth of the MCF10A human mammary epithelial cell line in vitro, but not to induce nude mouse tumorigenicity. Here we show that oncogene‐transformed MCF10A are able to halt in the lungs of nude mice, a sign of organ colonization potential. We have therefore studied the transformants for in vitro migratory and invasive properties known to correlate with the metastatic potential of human mammary carcinoma cells in nude mice. MCF10A transfected with Ha‐ras, infected with a recombinant retroviral vector containing the human c‐erbB‐2 proto‐oncogene (MCF10A‐HE cells), show a higher invasive index than either the single transfectant (MCF10A‐H) or MCF10A‐erbB‐2 (MCF10A‐E) cells in the Boyden chamber chemotaxis and chemoinvasion assays. The MCF10A‐HE cells also adopted an invasive stellate growth pattern when plated or embedded in Matrigel, in contrast to the spherical colonies formed by the single transformants MCF10A‐H, MCF10A‐E, and the parental cells. Dot‐blot analysis of gelatinase A and TIMP‐2 mRNA levels revealed increasing gelatinase A mRNA levels (HE > E > H > MCF10A) and reduced TIMP‐2 expression in both single and double transformants. Furthermore, MCF10A‐HE cells show more MMP‐2 activity than parental MCF 10A cells or the single transformants. CD44 analysis revealed differential isoform banding for the MCF10A‐HE cells compared to parental ceils, MCF10A‐H and MCF10A‐E, accompanied by increased binding of hyaluronan by the double transformants. Our results indicate that erbB‐2 and Ha‐ros co‐expression can induce a more aggressive phenotype in vitro, representative of the malignancy of mammary carcinomas. © 1995 Wiley‐Liss, Inc.

Original languageEnglish
Pages (from-to)815-822
Number of pages8
JournalInternational Journal of Cancer
Volume63
Issue number6
DOIs
Publication statusPublished - 1995

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Chara
Oncogenes
Phenotype
Nude Mice
Matrix Metalloproteinase 2
Breast Neoplasms
Messenger RNA
Chemotaxis
Hyaluronic Acid
Growth
Protein Isoforms
Breast
Epithelial Cells

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Invasive phenotype of MCF10A cells overexpressing c‐Ha‐ras and c‐erbB‐2 oncogenes. / Giunciuglio, Daniela; Culty, Martine; Fassina, Gianfranco; Masiello, Luciana; Melchiori, Antonella; Paglialunga, Giuseppina; Arand, Gloria; Ciardiello, Fortunato; Basolo, Fulvio; Thompson, Erik W.; Albini, Adriana.

In: International Journal of Cancer, Vol. 63, No. 6, 1995, p. 815-822.

Research output: Contribution to journalArticle

Giunciuglio, D, Culty, M, Fassina, G, Masiello, L, Melchiori, A, Paglialunga, G, Arand, G, Ciardiello, F, Basolo, F, Thompson, EW & Albini, A 1995, 'Invasive phenotype of MCF10A cells overexpressing c‐Ha‐ras and c‐erbB‐2 oncogenes', International Journal of Cancer, vol. 63, no. 6, pp. 815-822. https://doi.org/10.1002/ijc.2910630612
Giunciuglio, Daniela ; Culty, Martine ; Fassina, Gianfranco ; Masiello, Luciana ; Melchiori, Antonella ; Paglialunga, Giuseppina ; Arand, Gloria ; Ciardiello, Fortunato ; Basolo, Fulvio ; Thompson, Erik W. ; Albini, Adriana. / Invasive phenotype of MCF10A cells overexpressing c‐Ha‐ras and c‐erbB‐2 oncogenes. In: International Journal of Cancer. 1995 ; Vol. 63, No. 6. pp. 815-822.
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abstract = "Infection with erbB‐2 (E) of Ha‐roj (H) oncogene‐transfected cells has been previously shown to cooperatively induce anchorage‐independent growth of the MCF10A human mammary epithelial cell line in vitro, but not to induce nude mouse tumorigenicity. Here we show that oncogene‐transformed MCF10A are able to halt in the lungs of nude mice, a sign of organ colonization potential. We have therefore studied the transformants for in vitro migratory and invasive properties known to correlate with the metastatic potential of human mammary carcinoma cells in nude mice. MCF10A transfected with Ha‐ras, infected with a recombinant retroviral vector containing the human c‐erbB‐2 proto‐oncogene (MCF10A‐HE cells), show a higher invasive index than either the single transfectant (MCF10A‐H) or MCF10A‐erbB‐2 (MCF10A‐E) cells in the Boyden chamber chemotaxis and chemoinvasion assays. The MCF10A‐HE cells also adopted an invasive stellate growth pattern when plated or embedded in Matrigel, in contrast to the spherical colonies formed by the single transformants MCF10A‐H, MCF10A‐E, and the parental cells. Dot‐blot analysis of gelatinase A and TIMP‐2 mRNA levels revealed increasing gelatinase A mRNA levels (HE > E > H > MCF10A) and reduced TIMP‐2 expression in both single and double transformants. Furthermore, MCF10A‐HE cells show more MMP‐2 activity than parental MCF 10A cells or the single transformants. CD44 analysis revealed differential isoform banding for the MCF10A‐HE cells compared to parental ceils, MCF10A‐H and MCF10A‐E, accompanied by increased binding of hyaluronan by the double transformants. Our results indicate that erbB‐2 and Ha‐ros co‐expression can induce a more aggressive phenotype in vitro, representative of the malignancy of mammary carcinomas. {\circledC} 1995 Wiley‐Liss, Inc.",
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AU - Melchiori, Antonella

AU - Paglialunga, Giuseppina

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AU - Ciardiello, Fortunato

AU - Basolo, Fulvio

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