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Estrogen and progesterone receptors in transplantable Noble art mammary tumors Yeung, Chuck C. H.


The relationship between sex steroid hormone receptors and hormone dependent status of mammary tumors has been studied using an animal model. Hormone-induced Noble rat mammary tumor lines were maintained by serial transplantations. Transplants were carried out by injecting small pieces of viable tissues into the backs of animals. Depending on the hormonal status of the tumors, exogenous estrogen was supplemented. Tumors (5-10 g) were harvested and their cytoplasmic estrogen receptors (ERc), nuclear estrogen receptors (ERn) and cytoplasmic progesterone receptors (PgR) profiles were analyzed. The majority of the tumors studied did not depend on exogenous estrogen for growth i.e. they were hormone autonomous. They arose from transplants of a hormone dependent tumor, an autonomous tumor, or a tumor which had undergone a transition from dependency to autonomy upon removal of the exogenous estrogen source from the host. Histologically they appeared very homogeneous. Characterization of the receptor profiles of the autonomous tumors were intended to answer whether or not (1) the measurements of ERc, or ERn and PgR can indicate the autonomous status of these tumors (2) the levels of ERc, ERn and PgR are influenced by sequential transplantation (3) there is a change in the receptor profiles concurrent to tumor progression from dependency to autonomy. Receptors were measured by isolating the cytoplasmic and nuclear fractions prior to an exchange assay with radioactive hormone ligand. Cytoplasmic contamination of the ERn assay was avoided by the development of a procedure to isolate clean intact nuclei as starting material. Almost all of the autonomous tumors reported in this study (48 out of 52) have measurable amounts of cytoplasmic estrogen receptors (ERc+). This supports the general belief that ERc alone is not a sufficient indicator of hormone dependence. The level of receptors was also found to be quite constant in transplants over a number of generations of male and female hosts. This is consistent with the postulate that production of receptors is "genetically" coded by individual cell type and is not greatly influenced by the hormonal milieu. Noble rat mammary tumors began to progress towards autonomy when the estrogen pellets were removed. Changes in receptor profiles were studied with respect to tumor progression while under some degree of estrogen stimulation. Transplants were carried out in either intact female animals or males supplemented with an estrogen pellet, after the tumor had undergone a transition from dependency to autonomy. Results show that such tumors seemed to maintain an intact stimulatory pathway i.e. ERc+/ERn+/PgR+ if transplants were performed shortly after the removal of the estrogen pellets from the dependent tumors (<13 weeks). However, if duration of progression was extended, receptor profile would become negative and implied a total autonomous state. Therefore, it is suggested that tumor progression might be attenuated with hormone supplement. This would keep the estrogenic mechanism intact; thus maintaining an avenue for controlling growth via hormone manipulation. Two major groups of autonomous tumors with different receptor profiles were also observed. Group I tumours were shown to have measurable amounts of cytoplasmic estrogen receptors, nuclear estrogen receptors and cytoplasmic progesterone receptors (ERc+/ERn+/PgR+). Further investigation is necessary to elucidate whether these tumors might be hormone responsive thus required the maintenance of their estrogen stimulatory mechanism. In contrast, group II was ERc+/ERn +or- /PgR-. The absence of PgR in this group implies the presence of biochemical lesions or hormone nonresponsiveness and would agree with their autonomous behavior. This suggests that the measurement of PgR, which is believed to be an end product of estrogen- stimulation, might be more informative concerning the condition of the estrogenic stimulatory mechanism than the assays of ERc or ERn.

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