Required presence of both estrogen and pituitary factors for the growth of human breast cancer cells in athymic nude mice.

Estrogen, prolactin, and other pituitary factors are implicated in the etiology of human breast cancer. In the present study, the effects of estrogen and factors from GH3 rat pituitary tumor cells on the growth of T-47D human breast cancer cells were tested in athymic nude mice. Four groups of nude mice were used: Group 1 (T) received s.c. injection of T-47D cells only; Group 2 (TE) mice were given injections of estradiol valerate and T-47D cells; Group 3 mice were given injections of T-47D and GH3 cells (TG), one cell type on each flank; and Group 4 received estradiol valerate and T-47D and GH3 cells (TEG). We found that the human breast cancer cells, T-47D, did not proliferate in Groups 1 and 3 despite the presence of high circulating levels of prolactin and growth hormone produced by the growing GH3 pituitary tumors in Group 3. This suggested that prolactin and growth hormone were not sufficient to stimulate the growth of human breast cancer cells. T-47D cells exhibited only moderate growth in Group 2 but proliferated rapidly in Group 4. The T-47D tumors of Group 4 were 8 times larger than those in Group 2 after 42 days of growth. These results demonstrate that the simultaneous presence of estrogen and pituitary growth factors are required for maximal growth of T-47D human breast cancer cells in nude mice. The identity of the pituitary-dependent growth factor(S) that stimulates the growth in vivo of human breast cancer cells remains to be elucidated.