TY  - JOUR
AU  - Mandušić, Vesna
AU  - Nikolić-Vukosavljević, Dragica
AU  - Tanić, Nikola T
AU  - Kanjer, Ksenija
AU  - Nešković-Konstantinović, Zora B.
AU  - Celeketić, Dusica C
AU  - Dimitrijević, Bogomir B.
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1586
AB  - Purpose In addition to Estrogen Receptor alpha (ER alpha) and Progesterone Receptor (PR), the Second Estrogen Receptor (ER beta) appears to play an important role not only in estrogen signaling, but also in the pathogenesis of cancer in estrogen dependent tissues. The existence of various isoforms and splice variants of both ERs additionally complicates elucidation of their physiological role and involvement in the process of carcinogenesis. Methods In this study, the expression of ER beta 1 mRNA (wild type of beta receptor) and splice variant ER beta Delta 5 mRNA (which codes for truncated protein) was measured by the quantitative RT-PCR (q RT-PCR) in the 60 samples of Breast Cancer (BC) and correlated with ER alpha and PR protein levels and with clinical and histopathological parameters. Results We found the inverse correlation of ER beta Delta 5 mRNA expression with the levels of PR and ER alpha proteins in the group of postmenopausal patients; we also report the lower expression of ER beta 1 and ER beta Delta 5 mRNA in the larger tumors (>20 mm, T2, and T3) than in smaller ones (<= 20 mm, T1). The decrease of ER beta Delta 5 mRNA expression in larger tumors is found to arise from ER-positive breast carcinomas. In addition, the portion of tumors with concomitant high expression of both transcripts matches up the known percentage of tumors resistant to endocrine therapy in patients with different ER/PR status. Conclusions As far as we know, this is the first study in which ER beta Delta 5 mRNA splice variant was quantified by realtime RT-PCR in the clinical samples of breast cancer tissue. Until now, the focus of clinical reports was the level of ER beta 1, ER beta 2, and ER beta 5 isoforms. The higher expression of ER beta Delta 5 mRNA is associated with the indicators of low biological aggressiveness of tumor (low tumor size within ER-positive status in our study) suggesting that the uncontrolled local tumor growth may occur as the expression of ER beta Delta 5 mRNA decreases in estrogen-dependent breast cancer.
T2  - Journal of Cancer Research and Clinical Oncology
T1  - Expression of estrogen receptor beta wt isoform (ER beta 1) and ER beta Delta 5 splice variant mRNAs in sporadic breast cancer
IS  - 8
VL  - 133
EP  - 579
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1586
ER  - 

@article{
author = "Mandušić, Vesna and Nikolić-Vukosavljević, Dragica and Tanić, Nikola T and Kanjer, Ksenija and Nešković-Konstantinović, Zora B. and Celeketić, Dusica C and Dimitrijević, Bogomir B.",
year = "2007",
abstract = "Purpose In addition to Estrogen Receptor alpha (ER alpha) and Progesterone Receptor (PR), the Second Estrogen Receptor (ER beta) appears to play an important role not only in estrogen signaling, but also in the pathogenesis of cancer in estrogen dependent tissues. The existence of various isoforms and splice variants of both ERs additionally complicates elucidation of their physiological role and involvement in the process of carcinogenesis. Methods In this study, the expression of ER beta 1 mRNA (wild type of beta receptor) and splice variant ER beta Delta 5 mRNA (which codes for truncated protein) was measured by the quantitative RT-PCR (q RT-PCR) in the 60 samples of Breast Cancer (BC) and correlated with ER alpha and PR protein levels and with clinical and histopathological parameters. Results We found the inverse correlation of ER beta Delta 5 mRNA expression with the levels of PR and ER alpha proteins in the group of postmenopausal patients; we also report the lower expression of ER beta 1 and ER beta Delta 5 mRNA in the larger tumors (>20 mm, T2, and T3) than in smaller ones (<= 20 mm, T1). The decrease of ER beta Delta 5 mRNA expression in larger tumors is found to arise from ER-positive breast carcinomas. In addition, the portion of tumors with concomitant high expression of both transcripts matches up the known percentage of tumors resistant to endocrine therapy in patients with different ER/PR status. Conclusions As far as we know, this is the first study in which ER beta Delta 5 mRNA splice variant was quantified by realtime RT-PCR in the clinical samples of breast cancer tissue. Until now, the focus of clinical reports was the level of ER beta 1, ER beta 2, and ER beta 5 isoforms. The higher expression of ER beta Delta 5 mRNA is associated with the indicators of low biological aggressiveness of tumor (low tumor size within ER-positive status in our study) suggesting that the uncontrolled local tumor growth may occur as the expression of ER beta Delta 5 mRNA decreases in estrogen-dependent breast cancer.",
journal = "Journal of Cancer Research and Clinical Oncology",
title = "Expression of estrogen receptor beta wt isoform (ER beta 1) and ER beta Delta 5 splice variant mRNAs in sporadic breast cancer",
number = "8",
volume = "133",
pages = "579",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1586"
}

Mandušić, V., Nikolić-Vukosavljević, D., Tanić, N. T., Kanjer, K., Nešković-Konstantinović, Z. B., Celeketić, D. C.,& Dimitrijević, B. B.. (2007). Expression of estrogen receptor beta wt isoform (ER beta 1) and ER beta Delta 5 splice variant mRNAs in sporadic breast cancer. in Journal of Cancer Research and Clinical Oncology, 133(8).
https://hdl.handle.net/21.15107/rcub_ibiss_1586

Mandušić V, Nikolić-Vukosavljević D, Tanić NT, Kanjer K, Nešković-Konstantinović ZB, Celeketić DC, Dimitrijević BB. Expression of estrogen receptor beta wt isoform (ER beta 1) and ER beta Delta 5 splice variant mRNAs in sporadic breast cancer. in Journal of Cancer Research and Clinical Oncology. 2007;133(8):null-579.
https://hdl.handle.net/21.15107/rcub_ibiss_1586 .

Mandušić, Vesna, Nikolić-Vukosavljević, Dragica, Tanić, Nikola T, Kanjer, Ksenija, Nešković-Konstantinović, Zora B., Celeketić, Dusica C, Dimitrijević, Bogomir B., "Expression of estrogen receptor beta wt isoform (ER beta 1) and ER beta Delta 5 splice variant mRNAs in sporadic breast cancer" in Journal of Cancer Research and Clinical Oncology, 133, no. 8 (2007),
https://hdl.handle.net/21.15107/rcub_ibiss_1586 .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Niciforović, Ana
AU  - Vucić, Vesna
AU  - Nešković-Konstantinović, Zora B.
AU  - Spasić, Snezana D
AU  - Jones, David R
AU  - Radojcić, Marija B
AU  - Spasić, Mihajlo
PY  - 2006
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1655
AB  - There is a well-established role for reactive oxygen and nitrogen species, chronic inflammation and immune response in the pathogenesis of breast cancer. Complex interactions between breast cancer cells and surrounding blood vessels are prerequisites for cancer growth and invasion. Reports in the literature concerning the systemic response to, and the effect of, common breast cancer therapy on NF-kappa B and antioxidative defence enzyme expression and activity under clinical conditions are scarce. We determined these parameters in whole blood cell lysate from 16 women with breast cancer before and after combined (cyclophosphamide, doxorubicin, 5-fluorouracil; CAF) therapy and compared the results with 16 healthy women. Significantly higher levels of NF-kappa B and Mn-SOD (both their protein level and their activity) were found in breast cancer patients before and after CAF therapy, in comparison with healthy women. In parallel measurements, no change in the level or activity of catalase (CAT) was detected. According to our findings, it appears that breast cancer creates conditions that increase the level of hydrogen peroxide in the circulating cells and that the applied CAF therapy fails to compensate, therefore creating systemic conditions that favour survival and invasion of breast cancer cells.
T2  - Redox Report
T1  - Systemic NF-kappa B activation in blood cells of breast cancer patients
IS  - 1
VL  - 11
EP  - 44
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1655
ER  - 

@article{
author = "Adžić, Miroslav and Niciforović, Ana and Vucić, Vesna and Nešković-Konstantinović, Zora B. and Spasić, Snezana D and Jones, David R and Radojcić, Marija B and Spasić, Mihajlo",
year = "2006",
abstract = "There is a well-established role for reactive oxygen and nitrogen species, chronic inflammation and immune response in the pathogenesis of breast cancer. Complex interactions between breast cancer cells and surrounding blood vessels are prerequisites for cancer growth and invasion. Reports in the literature concerning the systemic response to, and the effect of, common breast cancer therapy on NF-kappa B and antioxidative defence enzyme expression and activity under clinical conditions are scarce. We determined these parameters in whole blood cell lysate from 16 women with breast cancer before and after combined (cyclophosphamide, doxorubicin, 5-fluorouracil; CAF) therapy and compared the results with 16 healthy women. Significantly higher levels of NF-kappa B and Mn-SOD (both their protein level and their activity) were found in breast cancer patients before and after CAF therapy, in comparison with healthy women. In parallel measurements, no change in the level or activity of catalase (CAT) was detected. According to our findings, it appears that breast cancer creates conditions that increase the level of hydrogen peroxide in the circulating cells and that the applied CAF therapy fails to compensate, therefore creating systemic conditions that favour survival and invasion of breast cancer cells.",
journal = "Redox Report",
title = "Systemic NF-kappa B activation in blood cells of breast cancer patients",
number = "1",
volume = "11",
pages = "44",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1655"
}

Adžić, M., Niciforović, A., Vucić, V., Nešković-Konstantinović, Z. B., Spasić, S. D., Jones, D. R., Radojcić, M. B.,& Spasić, M.. (2006). Systemic NF-kappa B activation in blood cells of breast cancer patients. in Redox Report, 11(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1655

Adžić M, Niciforović A, Vucić V, Nešković-Konstantinović ZB, Spasić SD, Jones DR, Radojcić MB, Spasić M. Systemic NF-kappa B activation in blood cells of breast cancer patients. in Redox Report. 2006;11(1):null-44.
https://hdl.handle.net/21.15107/rcub_ibiss_1655 .

Adžić, Miroslav, Niciforović, Ana, Vucić, Vesna, Nešković-Konstantinović, Zora B., Spasić, Snezana D, Jones, David R, Radojcić, Marija B, Spasić, Mihajlo, "Systemic NF-kappa B activation in blood cells of breast cancer patients" in Redox Report, 11, no. 1 (2006),
https://hdl.handle.net/21.15107/rcub_ibiss_1655 .

TY  - JOUR
AU  - Mandušić, Vesna
AU  - Nikolić-Vukosavljević, Dragica
AU  - Nešković-Konstantinović, Zora B.
AU  - Tanić, Nikola
AU  - Čeleketić, Dušica
AU  - Dimitrijević, Bogomir B.
PY  - 2006
PY  - 2006
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/374
AB  - Background: Estrogen and progesterone receptor (ER/PR) status is an accepted predictive marker in breast cancer. It is well known that breast tumors, which are ER(+) are more likely to respond to endocrine therapy. However, certain percentage of ER(+)/PR(+) tumors do not respond to endocrine therapy. Identification of the second estrogen receptor, named estrogen receptor beta (ERβ), as well as the existence of numerous isoforms/splice variants of both ERα and ERβ, suggests that complex regulation of estrogen action exists. In this study, we analyze does the expression of two ERβ isoforms correlates with ERα/PR status. Methods: Sixty samples of primary operable breast carcinomas were analyzed for ERα and PR protein levels and for mRNA expression of two ERβ isoforms (ERβ1 and ERβΔ5). ERα and PR proteins were measured by classical biochemical techniques, and ERβ mRNAs were measured by real-time RT-PCR. Results: Tumors are divided in three groups according to relative level of mRNA for ERβ1 and ERβΔ5. We found that there is no correlation of ERβ1 mRNA expression with ERα and PR protein levels. We confirmed the existence of inverse correlation of ERβΔ5 with PR and of ERβΔ5 with ERα in the group of postmenopausal patients. In the subsets of tumors defined by ERα/PR status, we found that percentage of tumors, which concomitantly expressed high levels of both transcripts, are parallel with those that do not response to tamoxifen treatment. Conclusion: Inverse correlation of ERα with ERβΔ5 and PR with ERβΔ5isoform suggests that ERβΔ5 may have inhibitory effect on ERα activity in postmenopausal patients. In addition, we point out that determination of expression profiles of ERα and ERβ isoforms in the defined groups of patient are necessary for elucidating its involvement in endocrine resistance.
T2  - Archive of Oncology
T1  - The role of estrogen receptors isoforms in breast cancer
IS  - 3-4
VL  - 14
SP  - 106
EP  - 109
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_374
ER  - 

@article{
author = "Mandušić, Vesna and Nikolić-Vukosavljević, Dragica and Nešković-Konstantinović, Zora B. and Tanić, Nikola and Čeleketić, Dušica and Dimitrijević, Bogomir B.",
year = "2006, 2006",
abstract = "Background: Estrogen and progesterone receptor (ER/PR) status is an accepted predictive marker in breast cancer. It is well known that breast tumors, which are ER(+) are more likely to respond to endocrine therapy. However, certain percentage of ER(+)/PR(+) tumors do not respond to endocrine therapy. Identification of the second estrogen receptor, named estrogen receptor beta (ERβ), as well as the existence of numerous isoforms/splice variants of both ERα and ERβ, suggests that complex regulation of estrogen action exists. In this study, we analyze does the expression of two ERβ isoforms correlates with ERα/PR status. Methods: Sixty samples of primary operable breast carcinomas were analyzed for ERα and PR protein levels and for mRNA expression of two ERβ isoforms (ERβ1 and ERβΔ5). ERα and PR proteins were measured by classical biochemical techniques, and ERβ mRNAs were measured by real-time RT-PCR. Results: Tumors are divided in three groups according to relative level of mRNA for ERβ1 and ERβΔ5. We found that there is no correlation of ERβ1 mRNA expression with ERα and PR protein levels. We confirmed the existence of inverse correlation of ERβΔ5 with PR and of ERβΔ5 with ERα in the group of postmenopausal patients. In the subsets of tumors defined by ERα/PR status, we found that percentage of tumors, which concomitantly expressed high levels of both transcripts, are parallel with those that do not response to tamoxifen treatment. Conclusion: Inverse correlation of ERα with ERβΔ5 and PR with ERβΔ5isoform suggests that ERβΔ5 may have inhibitory effect on ERα activity in postmenopausal patients. In addition, we point out that determination of expression profiles of ERα and ERβ isoforms in the defined groups of patient are necessary for elucidating its involvement in endocrine resistance.",
journal = "Archive of Oncology",
title = "The role of estrogen receptors isoforms in breast cancer",
number = "3-4",
volume = "14",
pages = "106-109",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_374"
}

Mandušić, V., Nikolić-Vukosavljević, D., Nešković-Konstantinović, Z. B., Tanić, N., Čeleketić, D.,& Dimitrijević, B. B.. (2006). The role of estrogen receptors isoforms in breast cancer. in Archive of Oncology, 14(3-4), 106-109.
https://hdl.handle.net/21.15107/rcub_ibiss_374

Mandušić V, Nikolić-Vukosavljević D, Nešković-Konstantinović ZB, Tanić N, Čeleketić D, Dimitrijević BB. The role of estrogen receptors isoforms in breast cancer. in Archive of Oncology. 2006;14(3-4):106-109.
https://hdl.handle.net/21.15107/rcub_ibiss_374 .

Mandušić, Vesna, Nikolić-Vukosavljević, Dragica, Nešković-Konstantinović, Zora B., Tanić, Nikola, Čeleketić, Dušica, Dimitrijević, Bogomir B., "The role of estrogen receptors isoforms in breast cancer" in Archive of Oncology, 14, no. 3-4 (2006):106-109,
https://hdl.handle.net/21.15107/rcub_ibiss_374 .