Estrogen-Induced Factors of Breast Cancer Cells Partially Replace Estrogen to Promote Tumor Growth

Dickson, Robert B.; McManaway, Mary E.; Lippman, Marc E.

doi:10.1126/science.3715461

Cited by 241 publications

(71 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Transforming growth factors (TGF alpha, TGF beta) are able to cause reversible phenotypic transformation of fibroblasts (Hsuan, 1989). In hormone dependent MCF-7 breast cancer cells, oestrogen-induced growth factors were identified that may have a role in growth control and might act as oestrogen-induced 'second messengers' in oestrogen-responsive growth of human breast cancer (Dickson et al, 1986;Knabbe et al, 1987). Our statistical analysis revealed an interdependence between the oestrogen receptor status of breast carcinomas and the ecto-5'-NT-expression of the adjacent stromal fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Expression of ecto-5'-nucleotidase (CD73) in normal mammary gland and in breast carcinoma

Krüger

Lf²,

Kaufmann³

et al. 1991

Br J Cancer

View full text Add to dashboard Cite

Summary Ecto-5'-nucleotidase (ecto-S'-NT) is a phosphatidylinositol anchored membrane structure recently defined as the lymphocyte differentiation antigen CD73. Using CD73 (I E9.28. 1) monoclonal antibody, normal mammary gland and breast carcinoma were immunohistochemically investigated for ecto-5'-NT expression. In normal breast epithelium, CD73 was differentially expressed in lobular, ductal and myoepithelial cells and was most frequently detected in the myoepithelial compartment. The glandular stroma contained fibrocytes, a subset of which was also CD73-positive. Among 102 unselected breast carcinoma primary lesions, only 9 contained CD73-positive tumour cells, whereas in 95 cases, stromal fibroblasts and fibrocytes showed variable degrees of CD73 expression. The extent of stromal CD73 expression correlated positively with the estrogen receptor (ER) status of the tumour (P < 0.038). We conclude that ecto-5'-NT-expression reflects a still unknown state of activity of normal breast epithelium which is lost in the majority of carcinomas derived therefrom. It may also be indicative of some functional activity of stromal fibroblasts which is significantly enhanced in ER-positive carcinomas.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of ecto-5'-nucleotidase (CD73) in normal mammary gland and in breast carcinoma

Krüger

Lf²,

Kaufmann³

et al. 1991

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Acquisition of an autocrine FGF growth loop would then free the cells from stromal control during tumor progression. Supporting this hypothesis is the ®nding that certain ER-negative breast tumor-derived cell lines express some of the FGFs (Dickson et al, 1986;Ethier, 1995); and MCF-7 cells transfected with a cDNA encoding FGF-4 formed tumors in ovariectomized mice (McLesky et al, 1993). These latter data contrast with our ®ndings, but it should be noted that the major di erence found by these authors between FGF-4-expressing MCF-7 and parental MCF-7 cells is the ability of the FGFexpressing cells to form tumors in vivo, where the angiogenic ability of FGFs could play a role.…”

Section: Mcf-7 T47dmentioning

confidence: 99%

“…Estrogen acts by activating the estrogen receptor (ER), a member of the nuclear receptor superfamily that dimerizes upon ligand binding, and regulates transcription from ERE (estrogen response element)-containing promoters in a cell-type speci®c manner (Tsai and O'Malley, 1994). The mechanism by which estrogen acts as a mitogen is still unclear; the consensus until recently was that its mitogenic e ect is partially mediated by the induction of growth factor signaling pathways (Dickson et al, 1986). Recent data however indicate that estrogen action may directly modulate the activity of cell cycle regulatory genes and cause phosphorylation of Rb (Altucci et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

FGF signaling activates STAT1 and p21 and inhibits the estrogen response and proliferation of MCF-7 cells

et al. 1998

View full text Add to dashboard Cite

Normal breast tissue as well as most breast tumors are dependent on estrogen for growth. Breast tumors often progress to a hormone-independent state which is associated with poor prognosis. It has been proposed that activation of growth factor signaling pathways in the tumor cells may free them from hormonal control. Certain growth factors can mimic estrogen responses by activating the estrogen receptor via its phosphorylation by mitogen-activated protein (MAP) kinase. In this report, however, we show that ®broblast growth factor (FGF), despite activating MAP kinase, is growthinhibitory for estrogen-dependent MCF-7 breast cancer cells. MCF-7 cells treated with FGFs exhibit slower growth than controls in both the presence and absence of estrogen, with a concomitant increase in the number of cells in G0/G1. Expression of a constitutively activated FGF receptor in these cells further decreases their growth rate, which is no longer in¯uenced by FGF treatment. Activation of the FGF signaling pathway also reduces the induction of an estrogen-responsive CAT reporter plasmid by estrogen, an e ect which appears to be independent of serine 118 in the estrogen receptor, a MAP kinase target site. The inhibitory e ects of FGF are probably mediated through the sustained induction of the cyclin kinase inhibitor p21/WAF1/CIP1, which is upregulated at the mRNA and protein level by FGF. FGF treatment also results in the phosphorylation of STAT1. This upregulation of p21 and phosphorylation of STAT1 is not detectable in T47D breast cancer cells upon which FGF has no inhibitory e ect.

show abstract

“…TGFα relates structurally to epidermal growth factor (EGF) [7] and binds to epidermal growth factor receptor (EGFR) on the cell surface [8]. Since the expression of TGFα is reported to be modulated by estrogen [9][10][11][12][13][14] and it is well established that ovariectomy (OVX) induces a marked involution of the mammary gland, we addressed the question whether the change in the TGFα level has a role in the mammary gland involution after OVX.…”

Section: Animals and Treatmentsmentioning

confidence: 99%

Effect of Ovariectomy on Mammary Gland Expression of TGF.ALPHA. and EGFR mRNAs and its Relation to Mammary Gland Involution in Mice.

Nagasawa

Ikezaki

Yamamoto

1998

Journal of Reproduction and Development

View full text Add to dashboard Cite

Abstract. To understand the relationship between transforming growth factor α (TGFα) and mammary gland involution, changes in the growth of normal and preneoplastic mammary glands, the expression of TGFα and epidermal growth factor receptor (EGFR) mRNAs in the mammary gland, and serum prolactin (PRL) level were examined in 3-month-old virgin SHN mice 4 to 108 days after ovariectomy (OVX). The formation of normal end-buds and preneoplastic hyperplastic alveolar nodules was significantly reduced after 9 days of OVX, associated with the decreased serum PRL level. Both TGFα and EGFR mRNA expression in the mammary glands declined 18 days after OVX. Thereafter, TGFα mRNA tended to increase, while EGFR mRNA continued to decrease. These observations suggest that the decline of both estrogen and PRL play major roles in the mammary gland involution after OVX, and that the decline of EGFR, through which TGFα manifests its effects, play a secondary role in this process. Key words: EGFR, Mammary gland, Mouse, Ovariectomy, TGFα.(J. Reprod. Dev. 44: [371][372][373][374][375] 1998) TGFα and EGFR mRNAs in the mammary gland and the growth of normal and preneoplastic mammary gland in OVX mice. We also examined the changes in serum prolactin (PRL) levels in these mice, since PRL is one of the key hormones necessary for mammary gland growth and secretion of PRL is largely controlled by ovarian estrogen [15]. Materials and Methods Animals and treatmentsAnimals used were virgin SHN/Mei mice maintained in our laboratory by strict brother × sister mating [16]. At 3 months of age, they were divided into two groups; the first group underwent a sham operation and served as the control. The ransforming growth factor α (TGFα) is a polypeptide which has been suggested to play

show abstract

Estrogen-Induced Factors of Breast Cancer Cells Partially Replace Estrogen to Promote Tumor Growth

Cited by 241 publications

References 9 publications

Expression of ecto-5'-nucleotidase (CD73) in normal mammary gland and in breast carcinoma

Expression of ecto-5'-nucleotidase (CD73) in normal mammary gland and in breast carcinoma

FGF signaling activates STAT1 and p21 and inhibits the estrogen response and proliferation of MCF-7 cells

Effect of Ovariectomy on Mammary Gland Expression of TGF.ALPHA. and EGFR mRNAs and its Relation to Mammary Gland Involution in Mice.

Contact Info

Product

Resources

About