Research experience
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Jan 1999–
Dec 2012Teaching: Universitat de les Illes Balears
Universitat de les Illes Balears · Departamento de Biología Fundamental y Ciencias de la SaludSpain · Palma
Publications (50) View all
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Article: The over-expression of ERbeta modifies estradiol effects on mitochondrial dynamics in breast cancer cell line.
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ABSTRACT: Mitochondrial biogenesis and function are under the control of 17β-estradiol, which acts through two distinct estrogen receptors (alpha or beta), and the estrogen receptors ratio can determine the final effect of 17β-estradiol on mitochondria. Our aim was to study the effects of 17β-estradiol on mitochondrial biogenesis, dynamics and function in breast cancer cell lines with different estrogen receptors ratios. Mitochondrial biogenesis was increased in MDA-MB-231 (with only estrogen receptor beta expression), T47D (normal estrogen receptors ratio) and MCF-7 (highest estrogen receptors ratio) breast cancer cell lines, in response to different mitochondrial and cellular status. In fact, mitochondria of the MDA-MB-231 and T47D cell lines maintained their functionality; although, the MCF-7 cell line did suffer an important decrease in mitochondrial function. Thus, mitochondrial biogenesis increased in MCF-7 with the aim of mitigating these defective mitochondria. In normal conditions, mitophagic processes remove defective mitochondria to refresh the mitochondrial pool. Mitochondrial dynamics were also under control by 17β-estradiol, and showed modifications in the fusion/fission processes and the modulation of mitochondrial removal. In fact, cells with only estrogen receptor beta or with a low estrogen receptors ratio, such as MDA-MB-231 and T47D, showed an increase in fusion processes. However, the MCF-7 cell line, with more estrogen receptor alpha, also showed an increase in fusion processes, even though the fission processes were diminished and led to an accumulation of unfunctional mitochondria. Finally, the importance of estrogen receptor beta in mitochondrial biogenesis, function, as well as in mitochondrial dynamics was examined. Using the T47D-estrogen receptor beta tetracycline-inducible cell line, the results confirmed that when the overexpression of estrogen receptor beta was inhibited, there was an increase in mitochondrial biogenesis, although these mitochondria were less functional, and with fewer fission events, although there was an increase in fusion processes.The international journal of biochemistry & cell biology 04/2013; · 4.89 Impact Factor -
Article: The oxidative stress in breast tumors of postmenopausal women is ERα/ERβ Ratio dependent.
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ABSTRACT: Estrogen receptor status is a diagnostic parameter in breast cancer treatment. Estrogen receptor presence is related to a better prognosis because the principal treatments attacking breast cancer tumors have their action site directed at the estrogen receptor. However, the two different subtypes of estrogen receptor, ERalpha and ERbeta, have different functions. In this work an alternative point of view focusing on oxidative stress is shown given that estrogen receptors regulate several proteins related to this oxidative stress such as: antioxidant enzymes, sirtuins and uncoupling proteins. Postmenopausal human breast tumors with a different ERalpha/ERbeta ratio were analyzed to characterize the amount of oxidative stress, mitochondrial function and the proliferation-related and oxidative stress-activated signaling pathways. Results showed that tumors with a low ERalpha/ERbeta ratio have greater oxidative damage and higher antioxidant enzyme protein levels as well as uncoupling protein and Sirtuin3 and have high studied signaling pathway activation. GPx, Complex V, Complex III, Complex II, Complex IV, AKT, SAPK and ERalpha were significantly and positively correlated with ERalpha/ERbeta ratio. However, Carbonyl groups, CAT, CuZn-SOD, UCP5, SIRT3 and ERbeta were significantly and negatively correlated with ERalpha/ERbeta Ratio. From the independent variables included in the step-by-step stepwise multiple linear regression analysis, only the ERalpha/ERbeta ratio was independently associated with carbonyl groups. Surprisingly, these low ERalpha/ERbeta ratio tumors have poor prognosis for the patient, and these results and those of other authors suggest that these tumors are adapted to conditions of increased oxidative stress.Free radical biology & medicine 03/2013; · 5.42 Impact Factor -
Article: Initial activation status of the antioxidant response determines sensitivity to carboplatin/paclitaxel treatment of ovarian cancer.
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ABSTRACT: Background/Aim: Ovarian carcinoma is the main cause of gynecological cancer related deaths. The aim of this study was to determine the activation status of the antioxidant response in samples of ovarian serous carcinoma from paraffin-embedded biopsies and compare them with the response of patients to carboplatin-paclitaxel treatment. Estrogen receptor alpha (ERα), antioxidant enzymes, and uncoupling protein (UCP) levels were analyzed by western blotting and the presence of estrogen receptor beta (ERβ) was investigated by immunohistochemistry (IHC). Lower levels of ERα, antioxidant enzymes and UCPs were found in patients resistant to treatment in comparison to the carboplatin/paclitaxel-sensitive ones; IHC revealed a greater presence of ERβ in sensitive patients. These results indicate that patients resistant to treatment have a lower level of antioxidant response activation compared to sensitive patients, fact which may be related to the efficacy of this treatment.Anticancer research 11/2012; 32(11):4723-8. · 1.73 Impact Factor -
Article: Mitochondrial dynamics is affected by 17β-estradiol in the MCF-7 breast cancer cell line. Effects on fusion and fission related genes.
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ABSTRACT: Mitochondrial dynamics, specifically fusion and fission processes, maintain mitochondria integrity and function, yet at this time, effect of estrogens on fusion and fission in breast cancer cell lines has not been studied. The aim of this study was to characterize the effect of 17β-estradiol on fusion and fission-related genes, as well as on mitochondria proliferation and function. We used MCF-7 breast cancer cell line, which is estrogen sensitive (estrogen receptor positive). Cells were grown in Dulbecco's modified Eagle medium charcoal-stripped fetal bovine serum and treated with 1nM of 17β-estradiol and with/without 100nM of ICI 182,780, a drug that caused rapid degradation of estrogen receptor. mRNA levels of fusion (mfn1, mfn2, opa1) and fission-related genes (drp1 and fis1) were examined by RT-PCR, cardiolipin content by N-acridyl-orange fluorescence and oxidative phosphorylation protein levels, as well as, the major fusion and fission related protein levels, by Western blot. mRNA expression of fusion-related genes increased after 17β-estradiol-treatment for 4h; however fis1 fission-related gene expression decreased. All these effects were not found in cells pre-treated with ICI 182,780, save for the changes in mfn-1, conferring them the effects of 17β-estradiol to estrogen receptor. The changes in protein levels were less prominent, but in the same way, than in mRNA levels, showing an increase in Mfn1 and Mfn2, as well as in Drp1, but there was no change in Fis1 protein levels. Mitochondrial biogenesis was also affected by 17β-estradiol, showing an increase in mtDNA but with no change in N-acridyl-orange fluorescence. On the whole, our results suggest an imbalance in the fusion/fission ratio, with a high fusion by 17β-estradiol-estrogen receptor action, which can affect to mitochondrial biogenesis, concretely in mitochondria proliferation. According to this information, 17β-estradiol would modify mitochondrial dynamics, biogenesis and metabolism, and thus compromise the normal development and function of mitochondria in cancer affected tissues.The international journal of biochemistry & cell biology 07/2012; 44(11):1901-5. · 4.89 Impact Factor -
Article: The ERalpha/ERbeta ratio determines oxidative stress in breast cancer cell lines in response to 17beta-estradiol.
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ABSTRACT: The effects of 17beta-estradiol (E2) are mediated through activation of estrogen receptors (ER): ERalpha and ERbeta. It is known that ERalpha/ERbeta ratio is higher in breast tumors than in normal tissue. Since antioxidant enzymes and uncoupling proteins (UCPs) are reactive oxygen species (ROS) production and mitochondrial biogenesis regulators, our aim was to study the E2-effect on oxidative stress, antioxidant enzyme expression, and UCPs in breast cancer cell lines with different ERalpha/ERbeta ratios. The lower ERalpha/ERbeta ratio T47D cell line showed low ROS production and high UCP5 levels. However, the higher ERalpha/ERbeta ratio MCF-7 cell line showed an up-regulation of antioxidant enzymes and UCPs, yet exhibited high oxidative stress. As a result, a decrease in antioxidant enzyme activities and UCP2 protein levels, coupled with an increase in oxidative damage was found. On the whole, these results show different E2-effects on oxidative stress regulation, modulating UCPs, and antioxidant enzymes, which were ERalpha/ERbeta ratio dependent in breast cancer cell lines.Journal of Cellular Biochemistry 05/2012; 113(10):3178-85. · 2.87 Impact Factor
