Expression of transforming growth factor alpha (TGF alpha) in differentiated rat mammary tumors: estrogen induction of TGF alpha production.
Expression of transforming growth factor alpha (TGF alpha) in differentiated rat mammary tumors: estrogen induction of TGF alpha production.
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DOI：
10.1210/mend-1-10-683
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发表时间：
1987-10
影响因子：
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通讯作者：
Sue C. Liu;Brunella Sanfilippo;Isabelle Perroteau;Rik Derynck;D. S. Salomon;W. Kidwell
中科院分区：
文献类型：
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作者：
Sue C. Liu;Brunella Sanfilippo;Isabelle Perroteau;Rik Derynck;D. S. Salomon;W. Kidwell
原发性分化良好的二甲苯α-蒽（DMBA）或亚硝基甲脲（NMU）诱导的雌激素依赖性大鼠乳腺腺癌具有生物活性和免疫反应性转化生长因子α（TGF α），这可以分别在分类琼脂生长促进试验和特异性液相竞争RIA中检测到。相反，从雌激素非依赖性和转移性的可移植未分化DMBA-I和NMU-II大鼠乳腺癌制备的组织提取物表现出低或不可检测的TGF α水平。此外，原发性DMBA和NMU诱导的大鼠乳腺癌表达特定的4.8-磷酸酶TGF α mRNA种类，而在可移植的DMBA-I和NMU-II肿瘤中很少或没有检测到TGF α mRNA。原发性肿瘤合成IV型基底膜胶原，而可移植性肿瘤产生非常少的IV型胶原。在正常小鼠乳腺上皮细胞的原代培养物中或在原代NMU诱导的肿瘤细胞中，TGF α或雌激素可以分别将IV型胶原的合成差异性地增强0.5至4倍于总蛋白质合成。因此，TGF-α可以作为一种雌激素诱导的自分泌生长因子的分化良好的大鼠乳腺肿瘤细胞的能力，选择性地调节IV型胶原蛋白的合成。雌激素可以调节TGF-α的产生在体内的主要DMBA诱导的大鼠乳腺肿瘤，因为卵巢切除术的结果在快速下降（6小时内）的TGF-α mRNA水平。这种对雌激素的反应也可以在体外观察到。原代DMBA或NMU诱导的大鼠乳腺肿瘤细胞在17 β-雌二醇（10（-8）M）存在下培养4天，显示TGF α mRNA水平高于未用雌激素处理的细胞。TGF α mRNA的这种增加被可检测到的免疫反应性TGF α水平和来自雌激素处理的细胞的条件培养基中的2- 3倍增加所抵消。这些结果表明，TGF-α可能是一个辅助标记的乳腺肿瘤，分化良好的腺癌和雌激素依赖性和雌激素非依赖性肿瘤不组成性产生TGF-α或表达TGF-α mRNA。
Primary well-differentiated dimethylbenzene alpha-anthracene (DMBA)-or nitrosomethylurea (NMU)-induced rat mammary adenocarcinomas that are estrogen dependent possess biologically active and immunoreactive transforming growth factor alpha (TGF alpha), which can be detected in a sort agar growth-promoting assay and by a specific liquid-phase competitive RIA, respectively. In contrast, tissue extracts prepared from transplantable undifferentiated DMBA-I and NMU-II rat mammary carcinomas that are estrogen independent and metastatic exhibit low or undetectable levels of TGF alpha. In addition, the primary DMBA- and NMU-induced rat mammary adenocarcinomas express a specific 4.8-kilobase TGF alpha mRNA species, whereas little or no TGF alpha mRNA can be detected in the transplantable DMBA-I and NMU-II tumors. Primary tumors synthesize type IV basement membrane collagen, whereas the transplantable tumors elaborate very little type IV collagen. Either TGF alpha or estrogens can differentially enhance the synthesis of type IV collagen by 0.5- to 4-fold over total protein synthesis in primary cultures of normal mouse mammary epithelial cells or in primary NMU-induced tumor cells, respectively. Therefore, TGF alpha could function as an estrogen-inducible autocrine growth factor for well differentiated rat mammary tumor cells by its ability to selectively regulate type IV collagen synthesis. Estrogens can modulate TGF alpha production in vivo in primary DMBA-induced rat mammary tumors, because ovariectomy results in a rapid decline (within 6 h) of TGF alpha mRNA levels. This response to estrogens can also be observed in vitro. Primary DMBA- or NMU-induced rat mammary tumor cells cultured in the presence of 17 beta-estradiol (10(-8) M) for 4 days show an increase in the level of TGF alpha mRNA over cells not treated with estrogen. This increase in TGF alpha mRNA is paralleled by a 2- to 3-fold increase in the levels of immunoreactive TGF alpha that can be detected and in the conditioned medium from estrogen-treated cells. These results suggest that TGF alpha may be an adjunct marker for those mammary tumors that are well differentiated adenocarcinomas and estrogen dependent and that estrogen-independent tumors do not constitutively produce TGF alpha or express TGF alpha mRNA.