Functional Significance of Selective Expression of ER&alpha; and ER&beta; in Mammary Gland Organ Culture

Rajendra G. Mehta

Functional Significance of Selective Expression of ERα and ERβ in Mammary Gland Organ Culture

Rajendra G. Mehta

Thoracic pair of mammary glands from steroid hormone-pretreated mice respond to hormones structurally and functionally in organ culture. A short exposure of glands for 24 h to 7,12 Dimethylbenz(a)anthracene (DMBA) during a 24-day culture period induced alveolar or ductal lesions. Methods: To differentiate the functional significance of ER&alpha: and ER&beta:, we employed estrogen receptor (ER) knockout mice. We compared the effects of DMBA on the development of preneoplastic lesions in the glands in the absence of ER&alpha: (&alpha:ERKO) and ER&beta: (&beta:ERKO) using an MMOC protocol. Glands were also subjected to microarray analyses. We showed that estradiol can be replaced by EGF for pretreatment of mice. The carcinogen-induced lesions developed under both steroids and EGF pretreatment protocols. The glands from &alpha:ERKO did not develop any lesions, whereas in &beta:ERKO mice in which ER&alpha: is intact, mammary alveolar lesions developed. Comparison of microarrays of control, &alpha:ERKO and &beta:ERKO mice showed that ER&alpha: was largely responsible for proliferation and the MAP kinase pathways, whereas ER&beta: regulated steroid metabolism-related genes. The results indicate that ER&alpha: is essential for the development of precancerous lesions. Both subtypes, ER&alpha: and Er&beta:, differentially regulated gene expression in mammary glands in organ cultures.

Показать больше [+]