Morphological phenotypes in neoplastic progression of human breast epithelial cells.

Neoplastic progression is a prolonged and stepwise process, while tumor growth occurs after a series of molecular alterations that culminate in tumorigenesis. The phenotypic changes of transformation in breast carcinogenesis were studied through the use of scanning and transmission electron microscopy. MCF 10F, a spontaneously immortalized human breast epithelial cell line (Soule et al., 1990), was treated with 7,12 dimethylbenz(a)anthracene (DMBA) (Calaf and Russo, 1993) and then transfected with the c-Ha-ras oncogene (Calaf et al., 1995). Treated cells showed a progression in altered morphology, anchorage independency, invasiveness and tumorigenicity in the SCID. Scanning and transmission electron microscopy illustrated that the transformed cells could be distinguished from control cells by the expression of morphological characteristics such as loss of contact inhibition, irregular size and shape, emission of long filopodia and formation of stratified layers. In contrast, control cells showed uniform, flattened and polyhedrical cells, well closely juxtaposed to each other and joined by cytoplasmic interdigitations. Control cells also did not form colonies in agar-methocel, and were not invasive or tumorigenic in SCID mice. These studies showed the progression of breast carcinogenesis by phenotypical changes induced by the carcinogen and the insertion of the c-Ha-ras oncogene.