Figure 4.

Decreased TGF-β responsiveness increases the tumor growth rate and histological grade of the low-grade breast carcinoma line M-III. (a) Tumor growth kinetics. Nude mice were inoculated subcutaneously on each hind flank with retrovirally transduced M-III cells (10⁶ cells/site; 10 sites/genotype). Untransduced parental M-III cells (n = 4, not shown) gave results essentially identical to M-III CON. (b–e). Histology of lesions formed by M-III transductants. Tumors of both genotypes were admixtures of three morphologic types. (b) M-III DNR tumor showing all three morphologies (Cr, cribriform structures; Cl, clear cells; At, area of atypia); (c) cribriform glands in an M-III CON tumor; (d) clear cell area in an M-III CON tumor; (e) area of atypia from an M-III DNR tumor. Magnification: ×100 (b) and ×400 (c–e). (f) Atypia and mitosis grades in M-III tumors. Histological sections were graded from 0 to 4 independently for extent of atypia and for frequency of mitoses as detailed in Methods. (g) Proliferation and apoptosis rates in M-III tumors. Tumor cell proliferation was quantitated by counting BrdU-labeled nuclei on histologic sections, and apoptotic cells were quantitated by TUNEL assay. Results are the mean ± SD for a minimum of five tumors of each genotype. PAR, parental untransduced cells; CON, cells transduced with pLPCX; DNR, cells transduced with pLPC-DNR. hpf, high-power field.