The multiple roles of Id-1 in cancer progression.

Abstract

Id-1 (Inhibitor of differentiation/DNA binding) is a member of the helix-loop-helix protein family expressed in actively proliferating cells. It regulates gene transcription by heterodimerization with the basic helix-loop-helix transcription factors and therefore inhibits them from DNA binding and transactivation of their target genes. Early studies showed that Id-1 functions mainly as a regulator in cellular differentiation of the muscle cells. The oncogenic role of Id-1 was revealed recently by the finding that Id-1 expression was able to induce cancer cell growth and promote cell survival. In addition, Id-1 protein was frequently overexpressed in over 20 types of cancer, supporting its role in the tumorigenesis of a wide range of tissues. However, the fact that Id-1 was able to activate multiple pathways involved in tumor progression suggests that Id-1 may in addition function in promotion of tumor development. For example, overexpression of Id-1 was found to induce expression of MT1-MMP protein, leading to invasion of breast cancer cells. A close association between Id-1 expression and angiogenesis has also been demonstrated recently in both normal and cancer cells. Accordingly, in prostate cancer cells, expression of Id-1 was able to activate EGF-R and nuclear factor-kappaB activities and resulted in progression to androgen independence. In addition, in both nasopharyngeal carcinoma and prostate cancer cells, Id-1 expression was found to protect the cells from chemotherapeutic drug-induced apoptosis through regulation of the Raf-1/MAPK and JNK pathways. This review will discuss recent evidence supporting the role of Id-1 in tumor progression and the mechanisms involved.

• Authors: Ming-Tat Ling, Xianghong Wang, Xiaomeng Zhang, Yong-Chuan Wong
• Journal: Differentiation; research in biological diversity (Differentiation) Vol. 74 Issue 9-10 Pg. 481-7 (Dec 2006) ISSN: 0301-4681 [Print] England
• PMID: 17177845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Inhibitor of Differentiation Protein 1

Topics

• Animals
• Apoptosis
• Cell Differentiation
• Disease Progression
• Drug Resistance, Neoplasm
• Humans
• Inhibitor of Differentiation Protein 1 (metabolism, physiology)
• Models, Biological
• Neoplasms (etiology, metabolism, therapy)