An expression study of hormone receptors in spontaneously developed, carcinogen-induced and hormone-induced mammary tumors in female Noble rats

Abstract

The Noble (Nb) rat model has been used in the study of hormonal carcinogenesis of mammary and prostate glands, as this rat strain is susceptible to tumor induction in these glands by hormonal treatments. Recently, we demonstrated that this rat strain can develop spontaneously mammary tumors at high incidence in aged animals and also show high sensitivity to chemical carcinogens (DMBA and MNU) and combined treatments with sex hormones in mammary tumor induction. In the present study, we examined and compared the expression of hormone receptors [including estrogen receptors (ERalpha and ERbeta), androgen receptor (AR), progesterone receptor (PR), prolactin receptor (PRLR)] and prolactin (PRL) by immunohistochemistry, Western blotting and RT-PCR in spontaneous mammary tumors, and mammary tumors induced by sex hormones (T+E2 and T+DES for 8-10 months) and DMBA in Nb rat model. Immunohistochemistry and Western blotting showed that both the spontaneously developed and hormone-induced carcinomas exhibited strong immunoreactivity of ERalpha, ERbeta, AR, PR and PRLR, while the spontaneous fibroadenomas showed weak to moderate immunoreactivity of ERalpha and PRLR, whereas the DMBA-induced carcinomas exhibited weak to moderate immunoreactivity of ERalpha, AR, PR and PRLR, and sporadic weak ERbeta immunoreactivity. RT-PCR analyses showed that mRNA expression pattern of these markers resembled that of proteins. In addition, weak mRNA expression of PRL was detected in spontaneous carcinomas and carcinomas induced by DMBA and hormones, suggesting that PRL could be produced locally within the tumors. The results showed that the expression status of hormone receptors and PRL was different in spontaneous mammary tumors and tumors induced by carcinogen or hormones, suggesting that the extent of involvement of steroid hormones and their receptors in the spontaneous, carcinogen- or hormone-induced mammary carcinogenesis might be different.