Amphiregulin mediates progesterone-induced mammary ductal development during puberty.
Amphiregulin mediates progesterone-induced mammary ductal development during puberty.
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DOI：
10.1186/bcr3431
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发表时间：
2013-05-25
期刊：
影响因子：
--
通讯作者：
Haslam SZ
中科院分区：
文献类型：
--
作者：
Aupperlee MD;Leipprandt JR;Bennett JM;Schwartz RC;Haslam SZ
青春期是对导致成年期乳腺癌风险增加的因素的易感性增加的时期。在青春期发育的乳腺终芽（EB）被认为是乳腺癌发生的靶点。虽然雌激素（E）在青春期乳腺发育中的作用已被广泛研究，但孕激素（P）在青春期的作用却不太明确。用溶剂对照（C）、E、P或E+ P处理青春期和青春期前卵巢切除小鼠。分析这些小鼠乳腺的形态学、增殖和下游靶点双调蛋白（AREG）和NF-κB配体受体激活剂（RANKL）表达的变化。P通过孕酮受体特异性作用，诱导乳腺增生和EB形成增加，这与导管和EB中AREG表达增加有关。E，通过雌激素受体特异性地发挥作用，产生类似的反应，也由AREG介导。用EGFR抑制剂阻断AREG作用完全消除了P对EB形成和增殖的影响，并显着降低了导管内的增殖。P也增加RANKL的表达，主要在导管中。RANK-Fc（一种RANKL抑制剂）治疗可降低导管中的P-依赖性增殖，并在较小程度上降低EB中的P-依赖性增殖，但不会导致EB消退。这些结果证明了一种新的P-特异性作用，通过AREG引起EB的形成和增殖，在发育中的乳腺在青春期之前和期间。因此，激素和/或因子除了E，上调AREG可以促进乳腺发育，并有可能影响乳腺癌的风险与青春期乳腺发育。
Puberty is a period of increased susceptibility to factors that cause increased breast cancer risk in adulthood. Mammary end buds (EBs) that develop during puberty are believed to be the targets of breast cancer initiation. Whereas the role of estrogen (E) has been extensively studied in pubertal mammary gland development, the role of progesterone (P) during puberty is less defined. Pubertal and prepubertal ovariectomized mice were treated with vehicle control (C), E, P, or E+P. Mammary glands from these mice were analyzed for changes in morphology, proliferation, and expression of the downstream targets amphiregulin (AREG) and receptor activator of NF-κB ligand (RANKL). P, acting specifically through the progesterone receptor, induced increases in mammary gland proliferation and EB formation that were associated with increased AREG expression in ducts and EBs. E, acting specifically through the estrogen receptor, produced similar responses also mediated by AREG. Blocking AREG action by treatment with an EGFR inhibitor completely abrogated the effect of P on EB formation and proliferation and significantly reduced proliferation within ducts. P also increased expression of RANKL, primarily in ducts. Treatment with RANK-Fc, an inhibitor of RANKL, reduced P-dependent proliferation in ducts and to a lesser extent in EB, but did not cause EB regression. These results demonstrate a novel P-specific effect through AREG to cause EB formation and proliferation in the developing mammary gland both before and during puberty. Thus, hormones and/or factors in addition to E that upregulate AREG can promote mammary gland development and have the potential to affect breast cancer risk associated with pubertal mammary gland development.
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影响因子：
4.8
作者：
Aupperlee, MD;Smith, KT;Haslam, SZ
通讯作者：
Haslam, SZ
影响因子：
2.5
作者：
Hovey, RC;Trott, JF;Vonderhaar, BK
通讯作者：
Vonderhaar, BK
DOI：
10.1007/bf00918341
发表时间：
1976-01-01
期刊：
TCA (Tissue Culture Association) Manual
影响因子：
--
作者：
BANERJEE M R;WOOD B G;CRUMP L R
通讯作者：
CRUMP L R
影响因子：
11.5
作者：
Johnston, SRD
通讯作者：
Johnston, SRD
DOI：
10.1073/pnas.0915148107
发表时间：
2010-02-16
影响因子：
11.1
作者：
Beleut, Manfred;Rajaram, Renuga Devi;Brisken, Cathrin
通讯作者：
Brisken, Cathrin