Prolactin overexpression by MDA-MB-435 human breast cancer cells accelerates tumor growth
Prolactin overexpression by MDA-MB-435 human breast cancer cells accelerates tumor growth
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DOI：
10.1023/a:1023956223037
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发表时间：
2003-05-01
影响因子：
3.8
通讯作者：
Ben-Jonathan, N
中科院分区：
文献类型：
--
作者：
Liby, K;Neltner, B;Ben-Jonathan, N
催乳素（PRL）是一种重要的激素在乳腺肿瘤的发生在啮齿动物，但其参与人类乳腺癌一直存在争议。局部产生的催乳素在乳腺癌发生中的作用是通过其对乳腺癌细胞的促有丝分裂作用以及催乳素及其受体（PRL-R）在乳腺癌中的表达而提出的。我们的目的是检查是否PRL，乳腺癌细胞过表达，形成一个自分泌/旁分泌环，赋予肿瘤的生长优势。产生过表达23 K人PRL的MDA-MB-435乳腺癌细胞，并通过RT-PCR、蛋白质印迹和Nb 2生物测定法确认克隆的PRL产生和分泌;对照克隆仅含有载体。在体外的23 K PRL克隆增殖速度更快，表达更高水平的PRL-R蛋白质比对照组只有当孵育在炭剥离血清（CSS）没有催乳激素。当注射到雌性裸鼠的乳房脂肪垫或皮下注射到雄性时，PRL过表达克隆形成的肿瘤比来自对照克隆或野生型MDA-MB-435细胞的肿瘤生长快2-4倍。Western分析显示，与对照肿瘤相比，PRL过表达的肿瘤中PRL、PRL-R和bcl-2水平显著更高。这些数据支持乳腺PRL作为生长/抗凋亡因子的作用，并表明其可作为治疗乳腺癌的新的治疗靶点。
Prolactin (PRL) is an important hormone in mammary tumorigenesis in rodents but its involvement in human breast cancer has been controversial. A role for locally produced PRL in breast carcinogenesis is suggested by its mitogenic action on breast cancer cells and the expression of both PRL and its receptor (PRL-R) in breast carcinomas. Our objective was to examine whether PRL, overexpressed by breast cancer cells, forms an autocrine/paracrine loop that confers a growth advantage for tumors. MDA-MB-435 breast cancer cells overexpressing 23K human PRL were generated, and PRL production and secretion by the clones were confirmed by RT-PCR, western blotting, and the Nb2 bioassay; control clones contain vector only. In vitro the 23K PRL clones proliferated faster and expressed higher levels of the PRL-R protein than controls only when incubated in charcoal-stripped serum (CSS) devoid of lactogenic hormones. When injected into the mammary fatpad of female nude mice or subcutaneously into males, the PRL-overexpressing clones formed tumors that grew 2-4-fold faster than tumors derived from control clones or wild type MDA-MB-435 cells. Western analysis demonstrated significantly higher PRL, PRL-R, and bcl-2 levels in the tumors overexpressing PRL compared to control tumors. These data support a role for breast PRL as a growth/anti-apoptotic factor and suggest that it may serve as a novel therapeutic target for the treatment of breast cancer.