Epidermal growth factor induces cyclin D1 in a human prostate cancer cell line

Abstract

BACKGROUND.The human prostate carcinoma cell line, LNCaP, proliferates under stimulation by a limited number of mitogenic signals, which include members of the growth factor and steroid hormone families. Androgens and epidermal growth factor (EGF) are among the LNCaP cell mitogens. We tested the hypothesis that these mitogens stimulate LNCaP cell proliferation at least in part through the induction of cyclin D 1 , a protein requisite for cell cycle progression, which is expressed in the G 1 phase of the cell cycle. METHODS. LNCaP cells were grown in serum-free medium with 10 ng/ml or 100 ng/ml EGF, 0.1 nM or 1.0 nM mibolerone (a potent androgen agonist), or vehicle (distilled water or 0.01% ethanol). Expression of cyclin D, mRNA, and protein were assessed by Northern and Western blot analyses. Transcription regulation was assessed by nuclear runoff assay. RESULTS. Western analyses demonstrated that EGF stimulated cyclin D 1 protein expression 4-fold over 12 hr. Northern analyses showed a 4-fold increase in mRNA expression, peaking within 4 hr of EGF stimulation. There were no effects on cyclin D 1 protein or mRNA expression with mibolerone treatments. We further explored the mechanism of cyclin D 1 induction. LNCaP cells stimulated for 1 hr with EGF demonstrated a 2-fold increase in cyclin D 1 message, as assayed by nuclear runoff transcription assay. In addition, we demonstrated the involvement of the protein kinase C pathway in mediating the EGF induction of cyclin D 1 . CONCLUSIONS. We conclude that one of the mechanisms by which growth factors such as EGF may stimulate prostate cell proliferation is through the direct induction of cyclin proteins, which are necessary for entry of cells into mitosis.

The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level

“…Cyclin D1 mRNA levels are increased in both primary prostate cancer samples (Han et al, 1998) and androgenindependent bone metastasis (Drobnjak et al, 2000). Furthermore, increased expression of cyclin D1 in LNCaP enhanced cell growth and tumorigenicity (Chen et al, 1998;Perry et al, 1998). Therefore, inhibition of cyclin D1 may be an interesting molecular target to control tumor proliferation (Zhang et al, 2007).…”

The Antidiabetic Drug Metformin Inhibits Gastric Cancer Cell Proliferation In Vitro and In Vivo

“…The role of EGFR activation in cell-cycle progression in some human cancers was studied. EGFR activation induced cyclin D1, a protein that is important in cell-cycle progression (26,27). Like EGFR, IGF-R1 has been shown to regulate both the expression and activity of many proteins involved in cell-cycle progression (28,29).…”

Photochemically stimulated drug delivery increases the cytotoxicity and specificity of EGF–saporin

“…Conventional chemotherapeutic agents such as the alkylating agents (cyclophosphoamide), antimetabolites (metotrexate) and cytotoxic antibiotics (bleomycin) exert their effect mainly on frequently dividing cancer cells. Severe adverse (Table 2), and activation of the receptor is associated with cancer cell related properties as increased proliferation (Perry et al 1998), blocking of apoptosis (Kulik et al 1997), migration (Woodburn 1999) and vascularisation (Schreiber et al 1986, Gille et al 1997 which make the receptor an interesting target for anti-cancer drugs. A recent report showed that EGFR also stimulate to survival of cancer cells independent of its kinase activity, by inhibiting autophagy (Weihua et al 2008).…”