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. (1995) Invasive phenotype of MCF10A cells overexpressing c-Ha-ras and c-erbB-2 oncogenes. International Journal of Cancer, 63(6), pp. 815-822.

View at publisher


Infection with erbB-2 (E) of Ha-ras (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-erB-2 proto-oncogene (MCF10A-HE cells), show a higher invasive index than either the single transfectant (MCF10A-H) or MCF10A-erB-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 MCF10A cells or the single transformants. CD44 analysis revealed differential isoform banding for the MCF10A-HE cells compared to parental cells, MCF10A-H and MCF10A-E, accompanied by increased binding of hyaluronan by the double transformants. Our results indicate that erB-2 and Ha-ras co-expression can induce a more aggressive phenotype in vitro, representative of the malignancy of mammary carcinomas.

Impact and interest:

43 citations in Scopus
Search Google Scholar™
59 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 72565
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):56
Export Date: 6 May 2014
Source: Scopus
PubMed ID: 8847140
Additional URLs:
DOI: 10.1002/ijc.2910630612
ISSN: 1097-0215
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 04 Jun 2014 04:00
Last Modified: 04 Jun 2014 04:00

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page