E2F activity is biphasically regulated by androgens in LNCaP cells.

Androgens exert a peculiar biphasic dose-dependent influence on the proliferation of LNCaP cells, a widely used model to study androgen effects on prostate cancer cells. Low concentrations of androgen stimulate proliferation, but high concentrations inhibit proliferation and induce strong expression of differentiation markers. In order to gain more insight into the molecular mechanisms that underlie these changes we studied the influence of a wide concentration range of the synthetic androgen R1881 on several cell cycle- and differentiation-related parameters. Low concentrations (0.1 nM), known to promote LNCaP cell proliferation, induce an increase of Retinoblastoma protein phosphorylation, accompanied by an increase of E2F-1 protein levels and E2F activity and by increased expression of the E2F-target gene products E2F-1 and cyclin A. High concentrations of R1881 (10 nM) induce strong expression of the differentiation marker prostate-specific antigen. Retinoblastoma protein is largely hypophosphorylated, resulting in low E2F activity and low concentrations of E2F-1 and cyclin A mRNA. Finally, there is a strong increase of p27(KIP1) protein, but not of p27(KIP1) mRNA. These results indicate that the biphasic dose response of LNCaP proliferation to androgen is closely reflected in Rb phosphorylation, E2F activity and p27(KIP1) protein expression.

Hofman K ，Swinnen JV ，Verhoeven G ，Heyns W ... -  《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》

Bone morphogenetic protein-2 induces hypophosphorylation of Rb protein and repression of E2F in androgen-treated LNCaP human prostate cancer cells.

Tomari K ，Kumagai T ，Shimizu T ，Takeda K ... -  《INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE》

Rb dephosphorylation and suppression of E2F activity in human breast tumor cells exposed to a pharmacological concentration of estradiol.

Gewirtz DA ，Di YM ，Randolph JK ，Jain PT ，Valerie K ，Bullock S ，Nath N ，Chellappan SP ... -  《ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS》

The cyclin-dependent kinase inhibitor (CDKI) flavopiridol disrupts phorbol 12-myristate 13-acetate-induced differentiation and CDKI expression while enhancing apoptosis in human myeloid leukemia cells.

Cartee L ，Wang Z ，Decker RH ，Chellappan SP ，Fusaro G ，Hirsch KG ，Sankala HM ，Dent P ，Grant S ... -  《CANCER RESEARCH》

Androgens repress Bcl-2 expression via activation of the retinoblastoma (RB) protein in prostate cancer cells.

Huang H ，Zegarra-Moro OL ，Benson D ，Tindall DJ ... -  《ONCOGENE》