The impact of endogenous estradiol metabolites on carcinogenesis

Lippert, T. H.; Seeger, Harald; Mueck, Alfred O.

doi:10.1016/s0039-128x(00)00101-x

Cited by 68 publications

(60 citation statements)

References 124 publications

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“…The extragenomic effect probably may prevail in women with breast cancer. It was proven by adding 16α-hydroxyestrone to the mammary epithelial gland culture, what induced uncontrolled cell proliferation [12]. What is more, an increased concentration of 16α-hydroxyestrone is observed in blood serum of women and urine of women with neoplasmatic disease of the mammary gland.…”

Section: Menopausal Periodmentioning

confidence: 99%

“…It was also stated, that intensity of hydroxylated C16-derivates of estrogens in relation to the C2-de rivatives is associated with the predisposition to breast cancer in man [12,13].…”

Section: Menopausal Periodmentioning

confidence: 99%

“…It was also found that progesterone plays a role in the proliferation of mammary gland cells. This steroid increases hydroxylation of estrone at C16 position in cultured breast cell lines [12]. 16α-hydroxyestrone induces proliferation and neoangiogenesis, the pro cesses involved in metastasis formation and spread of the neoplasm [14].…”

Section: Menopausal Periodmentioning

confidence: 99%

See 2 more Smart Citations

Physiology and pathology of the mammary gland in women in different periods of life (menopausal period and pregnancy)

Wróbel¹,

Putowski²,

Gogacz³

et al. 2013

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SummaryKnowledge of physiology of the mammary gland help us understand pathological processes which can occur in this organ, for example carcinogenesis. The results of epidemiological studies indicate an increased incidence of breast cancer in women receiving sex steroids, but the data concerning this issue are not unequivocal. The results of WHI (Women Health Initiative) and HERS (Heart and Estrogen/Progestin Replacement Study) studies point out to an elevated risk of neoplasia in the mammary gland among women taking hormone replacement therapy, which evokes a great deal of concern, uncertainty and fear both among doctors and patients. This fear should be replaced by the algorithm of professional medical management and a suitable choice of therapy in relation to a woman's age, genetic load, history of diseases and expected benefits. Directing a therapeutic option to the patient and supporting it with scientific data on HRT can convince women that the treatment will prevent, to a large extent, fractures, depression, Alzheimer's disease, colon cancer, stroke and heart attack. The risk of possible breast cancer death is much lower than compared to the affliction caused by estrogen depletion during early menopause. In the following review we present data which deal with physiology of the mammary gland in different periods of the woman's life, especially menopause. Moreover, the molecular mechanisms that may potentially play a role in neoplasia are discussed.Key words: mammary gland, breast cancer, hormone replacement therapy. StreszczenieZnajomość fizjologii gruczołu piersiowego kobiet pomaga w zrozumieniu mechanizmów odpowiedzialnych za rozwój procesów patologicznych tego gruczołu, w tym raka. Wyniki badań epidemiologicznych wskazują na wzrost częstości występowania raka piersi u kobiet przyjmujących hormony płciowe, ale dane dotyczące tej kwestii nie są jednoznaczne. Wyniki badań WHI (Women Health Initiative) i HERS (Heart and Estrogen/Progestin Replacement Study) zwracają uwagę na podwyższone ryzyko nowotworzenia w gruczole piersiowym w grupie kobiet stosujących hormonalną terapię zastępczą. Wywołuje to wiele niepokoju, niepewności i obaw zarówno wśród lekarzy, jak i pacjentek. Obawy te powinny zostać zastąpione przez profesjonalny algorytm postępowania i odpowiedni dobór terapii w zależności od wieku pacjentki, jej obciążenia genetycznego, chorób współistnieją-cych i spodziewanych korzyści dla układu kostnego, pokarmowego, nerwowego i krążenia. Odpowiednie przedstawienie tej opcji terapeutycznej i podparcie jej danymi naukowymi może przekonać kobiety do hormonalnej terapii zastępczej i wynikających z niej korzyści, takich jak zmniejszenie ryzyka wystąpienia złamania kości udowej, zapobieganie depresji i chorobie Alzheimera, profilaktyka raka jelita grubego, udaru i zawału serca. W niniejszej pracy zaprezentowano przegląd artykułów poruszających kwestię fizjologii gruczołu sutkowego w różnych okresach życia kobiety, poświęcając szczególną uwagę okresowi menopauzy. Ponadto przedstawiono mechanizmy molekularne, kt...

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Section: Menopausal Periodmentioning

confidence: 99%

“…It was also stated, that intensity of hydroxylated C16-derivates of estrogens in relation to the C2-de rivatives is associated with the predisposition to breast cancer in man [12,13].…”

Section: Menopausal Periodmentioning

confidence: 99%

Section: Menopausal Periodmentioning

confidence: 99%

See 1 more Smart Citation

Physiology and pathology of the mammary gland in women in different periods of life (menopausal period and pregnancy)

Wróbel¹,

Putowski²,

Gogacz³

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Breast cancer cells are often responsive to hormones, with estrogen and its metabolites being the most widely studied effectors. The cellular effects of estrogen have been implicated as possible factors in the induction and promotion of carcinogenesis (2). Additionally, estrogenic effects on cells have been demonstrated to decrease the efficacy of various chemotherapeutics and radiation therapy in vitro (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer

et al. 2006

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Abstract. Oncolytic herpes simplex virus-1 (HSV-1) mutants selectively replicate in and lyse tumor cells. Viral replication is dependent on the cellular proliferative mechanism. Estrogen increases cellular proliferation and decreases apoptosis in estrogen receptor-positive (ER + ) human breast cancer cells. We hypothesize that the cellular changes produced by estrogen may enhance oncolytic viral replication and improve the treatment of ER + breast cancer cells. Estrogen increased proliferation and replication of the HSV-1 mutant, NV1066, in ER + breast cancer cells. Additionally, cells grown with estrogen had lower rates of apoptosis and higher bcl-2 levels at baseline and after infection. Estrogen enhanced the oncolytic effect of NV1066, with cell kills of 95% and 97% at MOIs of 0.1 and 0.5, compared to 53 and 87% respectively without estrogen (p<0.001). Therapy of ER + human breast cancer cells with a replication-competent HSV-1 mutant is improved in the presence of estrogen, in contrast to more standard therapies, such as chemotherapy and radiation, which demonstrate decreased efficacy in similar conditions. These data provide the mechanistic basis for the use of oncolytic HSV-1 in patients with hormone receptor-positive breast cancer, particularly if the disease progresses with conventional therapies.

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“…The endogenous conversion of estradiol to its metabolites appears to contribute to the tumorigenic potential of estradiol (Schneider et al 1982, Lippert et al 2000. Estradiol (E 2 ) is metabolized primarily by hydroxylation at either the C-2 or the C-16 position ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Regulation of cell cycle and cyclins by 16alpha-hydroxyestrone in MCF-7 breast cancer cells

Js¹,

Thomas²,

Klinge³

et al. 2001

Journal of Molecular Endocrinology

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It has been suggested that alterations in estradiol (E 2 ) metabolism, resulting in increased production of 16 -hydroxyestrone (16 -OHE 1 ), is associated with an increased risk of breast cancer. In the present study, we examined the effects of 16 -OHE 1 on DNA synthesis, cell cycle progression, and the expression of cell cycle regulatory genes in MCF-7 breast cancer cells. G 1 synchronized cells were treated with 1 to 25 nM 16 -OHE 1 for 24 and 48 h. [ 3 H]Thymidine incorporation assay showed that 16 -OHE 1 caused an 8-fold increase in DNA synthesis compared with that of control cells, whereas E 2 caused a 4-fold increase. Flow cytometric analysis of cell cycle progression also demonstrated the potency of 16 -OHE 1 in stimulating cell growth. When G 1 synchronized cells were treated with 10 nM 16 -OHE 1 for 24 h, 62 3% of cells were in S phase compared with 14 3% and 52 2% of cells in the control and E 2 -treated groups respectively. In order to explore the role of 16 -OHE 1 in cell cycle regulation, we examined its effects on cyclins (D1, E, A, B1), cyclin dependent kinases (Cdk4, Cdk2), and retinoblastoma protein (pRB) using Western and Northern blot analysis. Treatment of cells with 10 nM 16 -OHE 1 resulted in 4-and 3-fold increases in cyclin D1 and cyclin A, respectively, at the protein level. There was also a significant increase in pRB phosphorylation and Cdk2 activation. In addition, transient transfection assay using an estrogen response element-driven luciferase reporter vector showed a 15-fold increase in estrogen receptor-mediated transactivation compared with control. These results show that 16 -OHE 1 is a potent estrogen capable of accelerating cell cycle kinetics and stimulating the expression of cell cycle regulatory proteins.

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The impact of endogenous estradiol metabolites on carcinogenesis

Cited by 68 publications

References 124 publications

Physiology and pathology of the mammary gland in women in different periods of life (menopausal period and pregnancy)

Physiology and pathology of the mammary gland in women in different periods of life (menopausal period and pregnancy)

Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer

Regulation of cell cycle and cyclins by 16alpha-hydroxyestrone in MCF-7 breast cancer cells

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