TRANSFORMING GROWTH-FACTOR-BETA-1, BETA-2, AND BETA-3, UROKINASE AND PARATHYROID HORMONE-RELATED PEPTIDE EXPRESSION IN 8701-BC BREAST-CANCER CELLS AND CLONES

8701-BC is a recently characterized cell line isolated from a primary ductal infiltrating carcinoma of the breast (d.i.c.), showing some ple omorphism in cell microanatomy at an ultrastructural level. We have ob tained different sublines of 8701-BC cells by cloning in soft agar at different concentrations (0.3% and 0.6%), and we have characterized th e cloned lines by some morphological and growth parameters. 8701-BC ce lls and clones have been submitted to analysis by reverse transcriptas e-linked polymerase chain reaction to detect mRNAs of various cytokine s (transforming growth factor-beta s, tumour necrosis factors, interle ukin 1s, interleukin 6, parathyroid hormone-related peptide, gamma int erferon) and of urokinase, which are bioactive molecules commonly invo lved in cell-cell and cell-stroma interactions at primary and/or secon dary sites of invasion. The aims of the present investigation were to determine: (a) if the corresponding genes are active in 8701-BC cell l ine and (b) if the sublines tested exhibit transcriptional heterogenei ty. The results obtained show that 8701-BC cells express transcripts o f transforming growth factor-beta s, urokinase and parathyroid hormone -related peptide (PTHrP), the latter product being responsible for the cancer-associated humoral hypercalcemic syndrome. Moreover, while the first two mRNAs are detectable in all the sublines tested, PTHrP is e xpressed almost uniquely by the clones isolated in 0.6% agar which exh ibit a peculiar morphological appearance, a higher growth rate and a m ore active invasive behaviour in vitro. The correlation between PTHrP expression and the potentially more aggressive subpopulation(s) of 870 1-BC cell line suggests the possibility to use also PTHrP as a marker of high risk of malignancy in breast carcinoma.