The role of CSF-1 in normal and neoplastic breast physiology.
The role of CSF-1 in normal and neoplastic breast physiology.
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DOI：
10.1046/j.1525-1373.1999.d01-1.x
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
E. Sapi;B. Kacinski
中科院分区：
文献类型：
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作者：
E. Sapi;B. Kacinski
集落刺激因子（CSF-1）及其受体（CSF-1 R，c-fms原癌基因的产物）最初被认为是正常单核细胞发育以及滋养层植入所必需的。然而，最近的研究结果表明，CSF-1和CSF-1 R可能在妊娠和哺乳期间的乳腺发育中具有额外的作用。对骨硬化（op-/op-）小鼠的研究表明，由于妊娠期间乳腺发育不完全，op-/op-母亲不能正常产奶，这些小鼠携带使CSF-1基因失活的特定突变。此外，在妊娠和哺乳期间，在乳腺上皮细胞中观察到CSF-1和CSF-1 R蛋白水平的显著增加。研究三种主要催乳激素（催乳素、胰岛素和糖皮质激素）对CSF-1和CSF-1 R表达的影响的体外研究表明，CSF-1的表达可受催乳素和胰岛素调节，而CSF-1 R的表达受糖皮质激素调节。CSF-1/CSF-1 R在正常乳腺发育中的这种明显作用是非常有趣的，因为已经发现这种受体/配体对在乳腺癌的生物学中也是重要的，其中它们通过尿激酶依赖性机制调节肿瘤细胞侵袭。本文综述了近年来关于CSF-1及其受体在正常和肿瘤性乳腺发育中的作用的研究结果，这些研究结果可能阐明生长因子诱导的乳腺生物学变化在妊娠期和肿瘤进展中的潜在关系。
Colony stimulating factor (CSF-1) and its receptor (CSF-1R, product of c-fms proto-oncogene) were initially implicated as essential for normal monocyte development as well as for trophoblastic implantation. However, recent findings have suggested that CSF-1 and CSF-1R might have additional roles in mammary gland development during pregnancy and lactation. Studies with osteopetrotic (op-/op-) mice, which bear a specific mutation that inactivates the CSF-1 gene, demonstrated that op-/op- mothers are incapable of normal milk production due to the incomplete development of their mammary glands during pregnancy. Also, significant increases in the levels of CSF-1 and CSF-1R proteins are observed in the epithelial cells of mammary gland during pregnancy and lactation. In vitro studies investigating the effect of the three major lactogenic hormones (prolactin, insulin, and glucocorticoids) on the expression of CSF-1 and CSF-1R have demonstrated that expression of CSF-1 can be regulated by prolactin and insulin whereas CSF-1R expression is regulated by glucocorticoids. This apparent role for CSF-1/CSF-1R in normal mammary gland development is very intriguing because this receptor/ligand pair has also been found to be important in the biology of breast cancer, where they regulate tumor cell invasion by a urokinase-dependent mechanism. This review aims to summarize recent findings on the role of CSF-1 and its receptor in normal and neoplastic mammary development which may elucidate potential relationships of growth factor-induced biological changes in the breast during pregnancy and tumor progression.