Ballin M, Mackay A R, Hartzler J L, Nason A, Pelina M D, Thorgeirsson U P
Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Clin Exp Metastasis. 1991 Mar-Apr;9(2):179-89. doi: 10.1007/BF01756388.
We have previously reported that activated ras oncogenes can simultaneously switch on the metastatic phenotype and increased capability to degrade type IV collagen. Here the relationship between c-H-ras, metalloproteinase expression and metastatic behavior was studied in N-nitrosomethylurea (NMU)-induced rat mammary carcinomas, which are known to possess activated c-H-ras. When comparing normal rat breast tissue to mammary carcinomas there was no direct relationship between ras DNA levels and neoplastic changes. Furthermore, there were no consistent differences between metastatic and non-metastatic carcinomas, or between primary tumors and metastases. The NMU-induced rat mammary carcinomas expressed two major gelatinolytic metalloproteinases (gelatinases) of 65 and 92 kD, but only the 65 kD gelatinase was detected in normal breast tissue and a rat fibroma. Type IV collagenolytic activity per 5 micrograms of protein was two to three times higher in the mammary carcinomas than in the normal breasts, whereas the primary tumors did not differ from the corresponding metastases. This study shows that ras amplification is not necessary for development of the malignant or metastatic phenotype in the NMU-induced rat mammary carcinoma model. We have also found that induction of p21 ras protein synthesis in a v-H-ras transfected NIH/3T3 (433) cell line, containing a glucocorticoid promoter, does not lead to an increase in metastatic capacity.
我们之前报道过，激活的ras癌基因可同时开启转移表型并增强降解IV型胶原的能力。在此，我们研究了在N-亚硝基甲基脲（NMU）诱导的大鼠乳腺癌中c-H-ras、金属蛋白酶表达与转移行为之间的关系，已知这些乳腺癌具有激活的c-H-ras。当将正常大鼠乳腺组织与乳腺癌进行比较时，ras DNA水平与肿瘤变化之间没有直接关系。此外，转移性和非转移性癌之间，或原发性肿瘤与转移灶之间没有一致的差异。NMU诱导的大鼠乳腺癌表达两种主要的明胶分解金属蛋白酶（明胶酶），分子量分别为65kD和92kD，但在正常乳腺组织和大鼠纤维瘤中仅检测到65kD的明胶酶。每5微克蛋白质的IV型胶原分解活性在乳腺癌中比在正常乳腺中高两到三倍，而原发性肿瘤与相应的转移灶没有差异。这项研究表明，在NMU诱导的大鼠乳腺癌模型中，ras扩增对于恶性或转移表型的发展不是必需的。我们还发现，在含有糖皮质激素启动子的v-H-ras转染的NIH/3T3（433）细胞系中诱导p21 ras蛋白合成，不会导致转移能力增加。
