LOSS OF CHROMOSOME 3P ARM DIFFERENTIATING TUMORIGENIC FROM NONTUMORIGENIC CELLS DERIVED FROM THE SAME SV40-TRANSFORMED HUMAN MAMMARY EPITHELIAL-CELLS

After immortalization of human normal mammary epithelial cells by replication-defective SV40 genome integration, 2 cultures were developed independently. Both had the same integration site, in band 9q21, but vapidly diverged karyotypically. After a few passages, one, designated SC2T2, exhibited near-diploid (a) and the other, designated SL2T2, near-tetraploid (b) karyotypes. The simplest formulas were 44, X, -X, der(3;22) (q10;q10), der(4) t(4;9)(q34;q12), +8, +9, add (13)(p1), der(19) t(8;19)(q21;p13.3), add (22)(p1)for karyotype (a) and 93, XXXX, add (1)(q12), add (11)(q13), +20 for karyotype (b). A number of alterations were further acquired with passages. Both cell cultures were tumorigenic, but their efficiency of grafting in nude mice largely differed: it was low for SL2T2 and high for SC2T2 cultures. All cultures of the xenografted tumors, obtained from either SL2T2 or SC2T2, exhibited the same clonal anomalies as those characterizing karyotype (a). It was concluded that only cells with karyotype (a) were tumorigenic, and that the difference in the tumorigenic potential of cultures SC2T2 and SL2T2 was related to their richness in cells with this karyotype. The comparison of the various karyotypes, together with data obtained in other cell types transformed by SV40, suggests that the acquisition of tumorigenicity in S2T2 mammary epithelial cells may be related to the loss of chromosome 3p arm. (C) 1995 Wiley-Liss, Inc.