The mechanism by which pharmacological concentrations of estrogen can paradoxically inhibit the growth of human breast cancer is unknown. We have selected for a variant line of MCF-7 which may help to understand this process. The variant was selected by exposing MCF-7 cells to high-specific-activity 16α-[125I]iodoestradiol. These cells were viably frozen for two isotopic half-lives, defrosted once, then reexposed to 16α-[125I]iodoestradiol to allow maximal radiation damage mediated by isotope associated with binding sites. This cell line (I13) is one of 55 lines cloned from MCF-7 cells that survived this treatment. The growth response to estradiol of the I13 breast cancer cells grown in monolayer is normal for 4 to 6 days, and then the cell number plateaus as the cells appear to round up and detach. Concomitantly, a decrease in [3H]thymidine incorporation occurs. The cells cannot be rescued by removing estradiol from the medium. The inhibition is dose dependent and can be seen in concentrations of estradiol as low as 10-10 M. The I13 cells are also inhibited by antiestrogens. They have normal levels of estrogen receptors which bind to DNA cellulose with activation. Progesterone receptors are estrogen inducible, although the levels are one-third that of wild-type MCF-7 cells. The morphological changes determined by electron microscopy of estrogen-treated cells are typical of degenerative cells. To investigate the possibility that inhibitory factors are secreted into the medium by I13 cells, conditioned medium from estrogen-exposed I13 cells is added to normal MCF-7 and I13 cells. No decrease in [3H]thymidine incorporation compared to controls is observed. When the secreted proteins are labeled with [35S]methionine and analyzed by sodium dodecyl sulfate-acrylamide gels, no major differences are apparent in the I13 and MCF-7 cells. Thus, the source of the defect is still unknown. It remains to be seen if the growth-inhibitory effects of 17β-estradiol on this cell line are receptor mediated or related to specific gene products which can be identified.
|Original language||English (US)|
|Number of pages||10|
|State||Published - Sep 1 1984|
ASJC Scopus subject areas
- Cancer Research