Role of Id-2 in the Maintenance of a Differentiated and Noninvasive Phenotype in Breast Cancer Cells

Yoko Itahana, Jarnail Singh, Tomoki Sumida, Jean Philippe Coppe, Simona Parrinello, James L. Bennington, Pierre Yves Desprez

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Id proteins are inhibitors of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. We have shown that ectopic expression of Id-1 in murine mammary epithelial cells resulted in loss of differentiation and gain of invasive and proliferative abilities. Moreover, Id-1 was highly expressed in aggressive breast cancer cells in culture and in biopsies from infiltrating carcinomas. In contrast to Id-1, we found that, in vitro and in vivo, Id-2 mRNA and protein were up-regulated as mammary epithelial cells lost proliferative capacity and initiated differentiation. We further determined that this up-regulation of Id-2 was a necessary step toward a fully differentiated phenotype in breast cells. Here we show that one of the components of the extracellular matrix network, laminin, is responsible for the increase in Id-2 expression during differentiation. We also show that Id-2 expression is inversely correlated with the rate of proliferation in murine mammary epithelial cells and that Id-2 is expressed at a higher level in differentiated human breast cancer cells in comparison with very aggressive and metastatic cells. When reintroduced in aggressive breast cancer cells, Id-2 is able to reduce their proliferative and invasive phenotypes and decrease their level of matrix metalloproteinase 9 secretion as well as increase syndecan-1 expression. Moreover, little Id-2 protein expression is detectable in human biopsies from aggressive and invasive carcinomas in comparison with in situ carcinomas. In conclusion, Id-2 expression not only follows a pattern opposite to that of Id-1 during mammary gland development and breast cancer progression but also appears to act as an important protein for the maintenance of a differentiated and noninvasive phenotype in normal and transformed breast cells.

Original languageEnglish
Pages (from-to)7098-7105
Number of pages8
JournalCancer Research
Volume63
Issue number21
Publication statusPublished - Nov 1 2003

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Breast
Maintenance
Breast Neoplasms
Phenotype
Epithelial Cells
Proteins
Syndecan-1
Basic Helix-Loop-Helix Transcription Factors
Carcinoma
Biopsy
Carcinoma in Situ
Matrix Metalloproteinase 9
Laminin
Human Mammary Glands
Extracellular Matrix
Up-Regulation
Cell Culture Techniques
Cell Proliferation
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Itahana, Y., Singh, J., Sumida, T., Coppe, J. P., Parrinello, S., Bennington, J. L., & Desprez, P. Y. (2003). Role of Id-2 in the Maintenance of a Differentiated and Noninvasive Phenotype in Breast Cancer Cells. Cancer Research, 63(21), 7098-7105.

Role of Id-2 in the Maintenance of a Differentiated and Noninvasive Phenotype in Breast Cancer Cells. / Itahana, Yoko; Singh, Jarnail; Sumida, Tomoki; Coppe, Jean Philippe; Parrinello, Simona; Bennington, James L.; Desprez, Pierre Yves.

In: Cancer Research, Vol. 63, No. 21, 01.11.2003, p. 7098-7105.

Research output: Contribution to journalArticle

Itahana, Y, Singh, J, Sumida, T, Coppe, JP, Parrinello, S, Bennington, JL & Desprez, PY 2003, 'Role of Id-2 in the Maintenance of a Differentiated and Noninvasive Phenotype in Breast Cancer Cells', Cancer Research, vol. 63, no. 21, pp. 7098-7105.
Itahana Y, Singh J, Sumida T, Coppe JP, Parrinello S, Bennington JL et al. Role of Id-2 in the Maintenance of a Differentiated and Noninvasive Phenotype in Breast Cancer Cells. Cancer Research. 2003 Nov 1;63(21):7098-7105.
Itahana, Yoko ; Singh, Jarnail ; Sumida, Tomoki ; Coppe, Jean Philippe ; Parrinello, Simona ; Bennington, James L. ; Desprez, Pierre Yves. / Role of Id-2 in the Maintenance of a Differentiated and Noninvasive Phenotype in Breast Cancer Cells. In: Cancer Research. 2003 ; Vol. 63, No. 21. pp. 7098-7105.
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