Wang B, Soule H D, Miller F R
Breast Cancer Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA.
Anticancer Res. 1997 Nov-Dec;17(6D):4387-94.
The ability of activated c-Ha-ras (codon 12 valine) to transform human breast epithelial cells varied for three different immortalized normal human breast epithelial cell lines established from two different women. Although activated c-Ha-ras may transform and induce a preneoplastic phenotype in MCF10A cells, activated c-Ha-ras was not sufficient to transform MCF10-2A cells. Only two of three MCF10-2A clones which expressed mutant p21 protein acquired the ability to form colonies in soft agar. When xenografted into nude beige mice, two MCF10-2A clones formed squamous carcinomas and one formed no lesions at all. The ability to form tumors did not correlate with growth in soft agar. All three activated c-Ha-ras-transfected clones of MCF-12A formed colonies in soft agar but only two produced squamous carcinomas in nude beige mice. Unlike activated c-Ha-ras-transfected MCF10A cells, none of the activated c-Ha-ras-transfected MCF10-2A or MCF-12A clones formed ducts in xenografts. Rather, initial xenograft lesions consisted of nests of cells with squamous differentiation. These observations illustrate that additional events are involved in the transformation and progression of human breast epithelial cells with activated c-Ha-ras.
从两名不同女性建立的三种不同的永生化正常人乳腺上皮细胞系中，激活的c-Ha-ras（密码子12缬氨酸）转化人乳腺上皮细胞的能力有所不同。尽管激活的c-Ha-ras可能会在MCF10A细胞中发生转化并诱导肿瘤前表型，但激活的c-Ha-ras不足以转化MCF10-2A细胞。在表达突变型p21蛋白的三个MCF10-2A克隆中，只有两个获得了在软琼脂中形成集落的能力。当异种移植到裸米色小鼠体内时，两个MCF10-2A克隆形成了鳞状癌，另一个则根本没有形成病变。形成肿瘤的能力与在软琼脂中的生长无关。所有三个激活的c-Ha-ras转染的MCF-12A克隆都在软琼脂中形成了集落，但只有两个在裸米色小鼠中产生了鳞状癌。与激活的c-Ha-ras转染的MCF10A细胞不同，激活的c-Ha-ras转染的MCF10-2A或MCF-12A克隆在异种移植中均未形成导管。相反，最初的异种移植病变由具有鳞状分化的细胞巢组成。这些观察结果表明，激活的c-Ha-ras在人乳腺上皮细胞的转化和进展中还涉及其他事件。
