The growth of MTW9 mammary
tumors exhibits different degrees of responsiveness to
ovariectomy, ranging from sensitivity to resistance. This range of response is a function of time elapsing from
tumor inoculation until performance of
ovariectomy provided that
prolactin (PRL) level is kept continuously high. In vivo studies showed that the MTW9
tumors developed by chronic administration of
spiramide were sensitive to
ovariectomy by 60 days, but they became resistant to
ovariectomy by 100 days. However, when
spiramide treatment was discontinued after
tumor appearance, the
tumors were still sensitive to
ovariectomy by 100 days. Chromatofocusing (CF) profile of cytosolic
estrogen receptors (ER) correlated with the responsiveness to
ovariectomy. A 2-peak profile for
tumors sensitive to
ovariectomy, and only a one-peak profile for
tumors resistant to
ovariectomy, were seen. Although the
prolactin level in rats bearing the
tumors was higher than in the normal rats, no correlation between the PRL level and the change in CF profile of ER over time was seen. Also, these changes could not be correlated with the
tumor size. In vitro studies showed that incubation of cytosolic ER from a sensitive
tumor (2 peaks) with PRL led to a CF profile with only one peak, characteristic of a resistant
tumor.
Leupeptin,
molybdate and phenylmethylsulfonylfluoride (PMSF) could not prevent this transition. The effect was not reproduced by incubation with
growth hormone or
progesterone. Our data suggest that PRL, either directly or through intermediates, may play a role in changing the response to hormonal
therapy of the mammary
tumor MTW9.