ID genes mediate tumor reinitiation during breast cancer lung metastasis Journal Article
| Authors: | Gupta, G. P.; Perk, J.; Acharyya, S.; De Candia, P.; Mittal, V.; Manova-Todorova, K.; Gerald, W. L.; Brogi, E.; Benezra, R.; Massague, J. |
| Article Title: | ID genes mediate tumor reinitiation during breast cancer lung metastasis |
| Abstract: | The establishment of distant metastases depends on the capacity of small numbers of cancer cells to regenerate a tumor after entering a target tissue. The mechanisms that confer this capacity remain to be defined. Here we identify a role for the transcriptional inhibitors of differentiation Id1 and Id3 as selective mediators of lung metastatic colonization in the triple negative [TN, i.e., lacking expression of estrogen receptor and progesterone receptor, and lacking Her2 (human epidermal growth factor receptor 2) amplification] subgroup of human breast cancer. Although broad expression of Id1 has recently been documented in tumors of the rare metaplastic subtype, here we report that rare Id1-expressing cells are also present in the more common TN subset of human breast tumors but not in other subtypes. We also provide evidence that Id1 expression is enriched in clinically obtained hormone receptor negative lung metastases. Functional studies demonstrate that Id1 and its closely related family member Id3 are required for tumor initiating functions, both in the context of primary tumor formation and during metastatic colonization of the lung microenvironment. In vivo characterization of lung metastatic progression reveals that Id1 and Id3 facilitate sustained proliferation during the early stages of metastatic colonization, subsequent to extravasation into the lung parenchyma. These results shed light on the proliferative mechanisms that initiate metastatic colonization, and they implicate Id1 and Id3 as mediators of this malignant function in the TN subgroup of breast cancers. © 2007 by The National Academy of Sciences of the USA. |
| Keywords: | controlled study; protein expression; human cell; cancer growth; nonhuman; cell proliferation; mouse; animals; mice; animal tissue; breast cancer; lung neoplasms; neoplasm proteins; animal experiment; animal model; in vivo study; breast neoplasms; carcinogenesis; mice, transgenic; lung metastasis; transplantation, heterologous; stem cells; microenvironment; inhibitor of differentiation protein 1; proliferation; hormone receptor; triple negative; inhibitor of differentiation protein; inhibitor of differentiation proteins; lung parenchyma |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 104 |
| Issue: | 49 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2007-12-04 |
| Start Page: | 19506 |
| End Page: | 19511 |
| Language: | English |
| DOI: | 10.1073/pnas.0709185104 |
| PUBMED: | 18048329 |
| PROVIDER: | scopus |
| PMCID: | PMC2148319 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 60" - "Export Date: 17 November 2011" - "CODEN: PNASA" - "Source: Scopus" |
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