Modulation of the proliferative response of breast cancer cells to growth factors by oestrogen

Abstract

SummaryA number of growth factors have been implicated in the control of the proliferation of breast cancer cells and some have been reported to mediate the proliferative effects of oestradiol. MCF-7 cells were treated with growth factors in the presence and absence of oestradiol. Oestradiol increased the response of cells to the proliferative effects of epidermal growth factor (EGF), transforming growth factor alpha (TGF-M) and basic fibroblast growth factor (bFGF). Platelet derived growth factor (PDGF) and cathepsin D had no effect in the presence or absence of oestradiol while TGF-P slightly reduced the stimulation by oestradiol. In the absence of oestradiol, there was little effect of combinations of growth factors although the effects of bFGF and IGF-I were additive. In the presence of oestradiol, the effects of bFGF and TGF-a were additive whereas bFGF acted as an IGF-I antagonist. Overall, bFGF had the greatest effect on cell proliferation although this was less marked than the previously described effect of the IGFs and insulin. (Lippman et al., 1976;Johnson et al., 1989). They therefore provide useful systems for studying the interactions between various growth factors and for understanding the mechanisms involved in the stimulation of proliferation by oestrogens and the interactions between growth factors and steroids.

Functional Rac-1 and Nck signaling networks are required for FGF-2-induced DNA synthesis in MCF-7 cells

“…E ect of FGF-2 on DNA synthesis in MCF-7 and MCF-7ras cells FGF-2 is known to be a mitogenic factor for serumdeprived MCF-7 cells (Karey and Sirbasku, 1988;Stewart et al, 1992). However, FGF-2, through its binding to FGFRs and activation of MAP kinase, inhibits growth of proliferating MCF-7 or MDA-MB-134 cells McLeskey et al, 1994).…”

“…These results suggest that Rac-1 is involved in DNA synthesis induced by FGF-2 in MCF-7 cells. 1988; Stewart et al, 1992). However, in proliferating MCF-7 cells, FGF-2 inhibition of DNA synthesis correlated with a sustained MAPK activation .…”

The IGF system and breast cancer.

“…An explanation for this may be that the expression of nearly all members of the IGF system is under transcriptional control of the ER. Thus, the ER regulates the transcription of IGF-I (Umayahara et al 1994), IGF-II (Osborne et al 1989, Lee et al 1994, IGF-IR (Stewart et al 1992), IGFBPs (McGuire et al 1992) and IRS-1 (Lee et al 1999, Salerno et al 1999, Molloy et al 2000.…”

“…In vitro, ER+ breast cancer cells like MCF-7, T47D and ZR-75 can be stimulated to proliferate by pico-or nanomolar concentrations of IGF-I and IGF-II (Karey & Sirbasku 1988), while ER-cells like MDA-MB231, MDA-435, MDA-468 are only minimally responsive or are not stimulated to proliferate by the IGFs. Furthermore, a synergy occurs between estradiol and IGF-I in mediating the proliferative response in ER+ cells (Stewart et al 1992). An explanation for this may be that the expression of nearly all members of the IGF system is under transcriptional control of the ER.…”

Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleotides to type I insulin-like growth factor receptor mRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor activity

“…Accumulating evidence has demonstrated interactions between ER and IGF-I/ IGF-IR signaling pathways (Stewart et al, 1990;Lee et al, 1999;Oesterreich et al, 2001). However, less information is available about cross-talks between IGF-IR and PR (Katzenellenbogen and Norman, 1990;Cho et al, 1994;Cui et al, 2003).…”