Activation of growth factor secretion in tumorigenic states of breast cancer induced by 17 beta-estradiol or v-Ha-ras oncogene.

Dickson, Robert B.; Kasid, Attan; Huff, Kenneth R.; Bates, Susan E.; Knabbe, Cornelius; Bronzert, Diane A.; Gelmann, Edward P.; Lippman, Marc E.

doi:10.1073/pnas.84.3.837

Cited by 167 publications

(62 citation statements)

References 31 publications

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“…It has been reported (Satoh et al, 1990;Dickson et al, 1987) that ras/p21 is involved in the intracellular pathway through which the EGF mitogenic signal is transduced. Moreover, high levels of EGFR are associated with a particularly poor prognosis in ovarian cancer (Scambia et al, 1992;Bartlett et al, 1996).…”

Section: Detection Of Point Mutationsmentioning

confidence: 99%

Prognostic significance of ras/p21 alterations in human ovarian cancer

Scambia

Masciullo²,

Panici³

et al. 1997

Br J Cancer

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Summary Ras/p21 oncoprotein expression and K-ras mutations were analysed by Western blot and/or K-ras oligonucleotide hybridization in 78 primary ovarian cancers, 20 omental metastases, two low malignant potential tumours (LMP), nine benign ovarian tumours and 10 normal ovaries. A cut-off value of an integral of absorbance (i.a.) of 2.20, obtained by receiver operating characteristic (ROC) curve, was shown to be the best cut-off for defining p21 positivity. p21 levels were higher in malignant tumours than in benign tumours (median 2.10 i.a. vs median 1.22 i.a.; P= 0.014) and in omental metastases than in primary ovarian carcinomas (median 2.54 i.a. vs median 2.1 i.a.; P= 0.0089). p21 overexpression did not correlate with any of the clinicopathological parameters examined. Follow-up data were available for 63 patients. A significant relationship was shown between p21 positivity and a shorter overall survival (OS) (P < 0.03) and progression-free survival (PFS) (P< 0.03). In multivariate analysis only the presence of ascites, p21 levels and epidermal growth factor receptor status retained an independent prognostic role. K-ras gene mutations were frequently detected in benign and low malignant potential tumours (71.4%), which were mostly mucinous (P= 0.01 52).

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Section: Detection Of Point Mutationsmentioning

confidence: 99%

Prognostic significance of ras/p21 alterations in human ovarian cancer

Scambia

Masciullo²,

Panici³

et al. 1997

Br J Cancer

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“…Among the oncogenes, c-Ha-Ras and Ras homologous A (Rho-A) from the Ras super family have been shown to promote both cell proliferation and invasion indicating their importance in malignant transformation (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). A critical step in the stimulation of cell surface receptors by their ligand involves the accumulation of Ras proteins in their active GTP-bound state.…”

Section: Introductionmentioning

confidence: 99%

Effect of curcumin on irradiated and estrogen-transformed human breast cell lines

Calaf

Echiburú-Chau²,

Wen³

et al. 2011

Int J Oncol

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Abstract. Curcumin (diferuloyl methane) is a well known antioxidant that exerts antiproliferative and apoptotic effects. Curcumin effect was evaluated in a breast cancer model that was developed using the immortalized breast epithelial cell line MCF-10F after exposure to low doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation, and subsequently cultured in the presence of 17β-estradiol (estrogen). This model consisted of human breast epithelial cells in different stages of transformation: i) MCF-10F; ii) Estrogen cell line; iii) a malignant Alpha3 cell line; iv) a malignant and tumorigenic, Alpha5 cell line; and v) a cell line derived from Alpha5 injected into the nude mice that gave rise to Tumor2 cell line. Curcumin decreased anchorage-independent growh in transformed breast cancer cell lines in comparison to their counterparts and increased the percentage of cells from G 0 /G 1 with a concomitant increase in G 2 /M phases, as well as a decrease in PCNA and Rho-A protein expression. Among the oncogenes, c-Ha-Ras and Ras homologous A (Rho-A) are important cell signaling factors for malignant transformation and to reach their active GTP bound state, Ras proteins must first release bound GDP mediated by a guanine nucleotide releasing factor (GRF). Then curcumin decrease RasGRF1 protein expression in malignant cell lines. Further, differential expression levels of cleaved (ADP) ribose polymerase 1 (PARP-1) and phosphorylated histone H2AX (γ-H2AX) were observed after curcumin treatment. It seems that PARP-1 similar to H2AX, confers cellular protection against radiation and estrogen-induced DNA damage mediated by curcumin. Therefore, targeting either PARP-1 or H2AX may provide an effective way of maximizing the therapeutic value of antioxidants for cancer prevention.

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“…Previous studies of our group emphasized the crucial role of TGF-b signaling in antiestrogen therapy and in the progression of breast cancer in general [6,[10][11][12][13]. By KaplanMeier analysis, we identified a correlation between the expression of TGF-b receptor II and a highly reduced overall survival in ER-negative breast cancer patients [14].…”

Section: Introductionmentioning

confidence: 79%

Estrogen receptor α attenuates transforming growth factor-β signaling in breast cancer cells independent from agonistic and antagonistic ligands

Stope

Popp²,

Knabbe³

et al. 2009

Breast Cancer Res Treat

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To investigate a presumed crosstalk between estrogen receptor a (ERa) and the TGF-b signaling pathway in breast cancer, we analyzed the TGF-b-induced expression of the plasminogen activator inhibitor 1 (PAI-1) gene in ER-positive MCF-7 cells. After siRNA-mediated knock-down of endogenous ERa, the transcription level of PAI-1 was upregulated, pointing to an attenuation of TGF-b signaling by the presence of ERa. We verified these findings by a vice versa approach using a primary ER-negative cell model transiently overexpressing either ERa or ERb. We found that ERa, but not ERb, led to a strong inhibition of the TGF-b1 signal, monitored by TGF-b reporter assays. This attenuation was completely independent of receptor stimulation by b-estradiol (E2) or inhibition by the pure antagonist ICI 182.780 (ICI). Our results indicate a permanent repression of PAI-1 by ERa and suggest a ligand-independent crosstalk between ERa and TGF-b signaling in breast cancer cells.

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Activation of growth factor secretion in tumorigenic states of breast cancer induced by 17 beta-estradiol or v-Ha-ras oncogene.

Cited by 167 publications

References 31 publications

Prognostic significance of ras/p21 alterations in human ovarian cancer

Prognostic significance of ras/p21 alterations in human ovarian cancer

Effect of curcumin on irradiated and estrogen-transformed human breast cell lines

Estrogen receptor α attenuates transforming growth factor-β signaling in breast cancer cells independent from agonistic and antagonistic ligands

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