de Candia Paola, Benera Robert, Solit David B
Memorial Sloan-Kettering Cancer Center, Program in Cell Biology and Department of Medicine, New York, New York 10021, USA.
Adv Cancer Res. 2004;92:81-94. doi: 10.1016/S0065-230X(04)92004-0.
Id helix-loop-helix (HLH) proteins are regulators of cell growth and differentiation in embryonic and adult tissues. They are members of the basic HLH family of transcription factors but lack a DNA binding domain. By binding to basic HLH transcription factors, Id proteins regulate gene expression. Id1 and Id3 have extensive sequence homology and similar patterns of expression during embryogenesis and in adult tissues. They are also expressed at high levels in the endothelial cells of tumor-infiltrating blood vessels, and breast tumors spontaneously arising in MMTV-neu mice demonstrate impaired angiogenesis when growing in an Id1- and/or Id3-deficient background. These lesions are typically cystic with a small rim of viable tumor cells surrounding an acellular necrotic core. Id2 plays a critical role in breast differentiation and lactation. Id4 regulates BRCA1 expression and may be involved in hormone-dependent regulation of BRCA1 homeostasis. Thus, all four members of the Id protein family play pivotal roles in distinct aspects of normal and malignant breast biology, the subject of this review.
Id螺旋-环-螺旋（HLH）蛋白是胚胎和成年组织中细胞生长与分化的调节因子。它们是基本HLH转录因子家族的成员，但缺乏DNA结合结构域。通过与基本HLH转录因子结合，Id蛋白调节基因表达。Id1和Id3具有广泛的序列同源性，并且在胚胎发育过程中和成年组织中有相似的表达模式。它们在肿瘤浸润血管的内皮细胞中也高水平表达，并且在MMTV-neu小鼠中自发产生的乳腺肿瘤在Id1和/或Id3缺陷背景下生长时显示出血管生成受损。这些病变通常是囊性的，在无细胞坏死核心周围有一小圈存活的肿瘤细胞。Id2在乳腺分化和泌乳中起关键作用。Id4调节BRCA1的表达，可能参与BRCA1稳态的激素依赖性调节。因此，Id蛋白家族的所有四个成员在正常和恶性乳腺生物学的不同方面都起着关键作用，这是本综述的主题。
