Dynamics of notch expression during murine prostate development and tumorigenesis

Notch signaling has been widely demonstrated to be responsible for cell fat e determination during normal development and implicated in human T-cell le ukemia and mouse mammary carcinomas. Here we show that Notch signaling may be involved in prostatic development and cancer cell growth. In situ hybrid ization and reverse transcription-PCR analyses revealed that Notch1 was exp ressed in prostate epithelial cells during normal development and in prosta te cancer cells. Characterization of Notch1-green fluorescent protein trans genic mice, in which the expression of reporter green fluorescent protein i s under the control of the Notch1 promoter, indicated that Notch1-expressin g cells were associated with the basal epithelial cell population in the pr ostate. Examination of the transgenic adenocarcinoma of the mouse prostate showed that expression of Notch1 was elevated in malignant prostatic epithe lial cells of primary and metastatic tumors. Expression of Notch ligands, h owever, was low or undetectable in cultured prostate cancer cells or in mal ignant prostatic epithelial cells in transgenic adenocarcinoma of the mouse prostate. Furthermore, overexpression of a constitutively active form of N otch1 inhibited the proliferation of various prostate cancer cells, includi ng DU145, LNCaP, and PC3 cells. Taken together, our data indicate for the f irst time that Notch signaling may play a role in murine prostatic developm ent and tumorigenesis.