TY  - JOUR
AU  - Tanić, Nikola T
AU  - Milovanović, Zorka
AU  - Tanić, Nasta
AU  - Džodić, Radan R.
AU  - Juranić, Zorica D
AU  - Susnjar, Snezana
AU  - Plesinac-Karapandžić, Vesna
AU  - Tatić, Svetislav B
AU  - Dramicanin, Tatjana
AU  - Davidović, Radoslav
AU  - Dimitrijević, Bogomir B.
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1100
AB  - Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.
T2  - Cancer Biology & Therapy
T1  - The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients
IS  - 12
VL  - 13
SP  - 55
EP  - 1174
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1100
ER  - 

@article{
author = "Tanić, Nikola T and Milovanović, Zorka and Tanić, Nasta and Džodić, Radan R. and Juranić, Zorica D and Susnjar, Snezana and Plesinac-Karapandžić, Vesna and Tatić, Svetislav B and Dramicanin, Tatjana and Davidović, Radoslav and Dimitrijević, Bogomir B.",
year = "2012",
abstract = "Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.",
journal = "Cancer Biology & Therapy",
title = "The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients",
number = "12",
volume = "13",
pages = "55-1174",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1100"
}

Tanić, N. T., Milovanović, Z., Tanić, N., Džodić, R. R., Juranić, Z. D., Susnjar, S., Plesinac-Karapandžić, V., Tatić, S. B., Dramicanin, T., Davidović, R.,& Dimitrijević, B. B.. (2012). The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients. in Cancer Biology & Therapy, 13(12), 55-1174.
https://hdl.handle.net/21.15107/rcub_ibiss_1100

Tanić NT, Milovanović Z, Tanić N, Džodić RR, Juranić ZD, Susnjar S, Plesinac-Karapandžić V, Tatić SB, Dramicanin T, Davidović R, Dimitrijević BB. The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients. in Cancer Biology & Therapy. 2012;13(12):55-1174.
https://hdl.handle.net/21.15107/rcub_ibiss_1100 .

Tanić, Nikola T, Milovanović, Zorka, Tanić, Nasta, Džodić, Radan R., Juranić, Zorica D, Susnjar, Snezana, Plesinac-Karapandžić, Vesna, Tatić, Svetislav B, Dramicanin, Tatjana, Davidović, Radoslav, Dimitrijević, Bogomir B., "The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients" in Cancer Biology & Therapy, 13, no. 12 (2012):55-1174,
https://hdl.handle.net/21.15107/rcub_ibiss_1100 .

TY  - JOUR
AU  - Damjanović, Svetozar S
AU  - Antić, Jadranka A
AU  - Ilić, Bojana B
AU  - Beleslin-Cokić, Bojana B
AU  - Ivović, Miomira S
AU  - Ognjanović, Sanja I
AU  - Isailović, Tatjana V
AU  - Popović, Bojana M
AU  - Bozić, Ivana B
AU  - Tatić, Svetislav B
AU  - Matić, Gordana
AU  - Todorović, Vera N
AU  - Paunović, Ivan R
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1085
AB  - Glucocorticoid (GC) sensitivity depends on glucocorticoid receptor (GR) and heat shock proteins (Hsps). We investigated whether common GR genes (ER22/23EK N363S, BclI, and 9 beta) and adrenocorticotropin receptor promoter polymorphisms influence susceptibility for unilateral adrenal incidentaloma (AI), plus GR and Hsp expression in tumorous (n = 19), peritumorous (n = 13) and normal adrenocortical (n = 11) tissues. Patients (n = 112), population-matched controls (n = 100) and tumor tissues (n = 32) were genotyped for these polymorphisms. Postdexamethasone serum cortisol was higher in patients (p<0.001). GR gene variants, larger allele of BclI (odds ratio (OR) 2.9; 95% confidence interval (CI) 1.7-5.1; p < 0.001) and minor allele of 9 beta (OR 3.0; 95% CI 1.6-5.7; p < 0.001) were independent predictors of Al. In patients, the first allele is linked with larger tumors (p = 0.002) and the latter with higher postdexamethasone cortisol levels (p = 0.025). Both allele carriers had lesser waist circumference (p = 0.02), similar adrenocorticotropin and higher basal (p = 0.024) and postdexamethasone cortisol concentrations (p < 0.001). Tumorous and constitutional genotypes were similar. GR-D is the major receptor isoform in normal adrenal cortex by Western blotting. Loss of other receptor isoforms, decrease in immunostaining for GR (p < 0.0001), underexpression of chaperones (p <= 0.01) and the presence of inducible Hsp70 were found in adenomas. In conclusion, GR gene variants, C allele of BclI and minor allele of 9 beta, are associated with Als. Their concurrent presence in patients reduces GC sensitivity Normal adrenal cortex preferentially expresses GR-D. In adenomas, the lack of other GR isoforms and underexpression of heat shock proteins perhaps permanently impair GC signaling, which could promote dysregulated cortisol production and tumor growth. The innate GC sensitivity probably modifies these effects. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00261
T2  - Molecular Medicine
T1  - Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids
IS  - 11
VL  - 18
SP  - 189
EP  - 1465
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1085
ER  - 

@article{
author = "Damjanović, Svetozar S and Antić, Jadranka A and Ilić, Bojana B and Beleslin-Cokić, Bojana B and Ivović, Miomira S and Ognjanović, Sanja I and Isailović, Tatjana V and Popović, Bojana M and Bozić, Ivana B and Tatić, Svetislav B and Matić, Gordana and Todorović, Vera N and Paunović, Ivan R",
year = "2012",
abstract = "Glucocorticoid (GC) sensitivity depends on glucocorticoid receptor (GR) and heat shock proteins (Hsps). We investigated whether common GR genes (ER22/23EK N363S, BclI, and 9 beta) and adrenocorticotropin receptor promoter polymorphisms influence susceptibility for unilateral adrenal incidentaloma (AI), plus GR and Hsp expression in tumorous (n = 19), peritumorous (n = 13) and normal adrenocortical (n = 11) tissues. Patients (n = 112), population-matched controls (n = 100) and tumor tissues (n = 32) were genotyped for these polymorphisms. Postdexamethasone serum cortisol was higher in patients (p<0.001). GR gene variants, larger allele of BclI (odds ratio (OR) 2.9; 95% confidence interval (CI) 1.7-5.1; p < 0.001) and minor allele of 9 beta (OR 3.0; 95% CI 1.6-5.7; p < 0.001) were independent predictors of Al. In patients, the first allele is linked with larger tumors (p = 0.002) and the latter with higher postdexamethasone cortisol levels (p = 0.025). Both allele carriers had lesser waist circumference (p = 0.02), similar adrenocorticotropin and higher basal (p = 0.024) and postdexamethasone cortisol concentrations (p < 0.001). Tumorous and constitutional genotypes were similar. GR-D is the major receptor isoform in normal adrenal cortex by Western blotting. Loss of other receptor isoforms, decrease in immunostaining for GR (p < 0.0001), underexpression of chaperones (p <= 0.01) and the presence of inducible Hsp70 were found in adenomas. In conclusion, GR gene variants, C allele of BclI and minor allele of 9 beta, are associated with Als. Their concurrent presence in patients reduces GC sensitivity Normal adrenal cortex preferentially expresses GR-D. In adenomas, the lack of other GR isoforms and underexpression of heat shock proteins perhaps permanently impair GC signaling, which could promote dysregulated cortisol production and tumor growth. The innate GC sensitivity probably modifies these effects. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00261",
journal = "Molecular Medicine",
title = "Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids",
number = "11",
volume = "18",
pages = "189-1465",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1085"
}

Damjanović, S. S., Antić, J. A., Ilić, B. B., Beleslin-Cokić, B. B., Ivović, M. S., Ognjanović, S. I., Isailović, T. V., Popović, B. M., Bozić, I. B., Tatić, S. B., Matić, G., Todorović, V. N.,& Paunović, I. R.. (2012). Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids. in Molecular Medicine, 18(11), 189-1465.
https://hdl.handle.net/21.15107/rcub_ibiss_1085

Damjanović SS, Antić JA, Ilić BB, Beleslin-Cokić BB, Ivović MS, Ognjanović SI, Isailović TV, Popović BM, Bozić IB, Tatić SB, Matić G, Todorović VN, Paunović IR. Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids. in Molecular Medicine. 2012;18(11):189-1465.
https://hdl.handle.net/21.15107/rcub_ibiss_1085 .

Damjanović, Svetozar S, Antić, Jadranka A, Ilić, Bojana B, Beleslin-Cokić, Bojana B, Ivović, Miomira S, Ognjanović, Sanja I, Isailović, Tatjana V, Popović, Bojana M, Bozić, Ivana B, Tatić, Svetislav B, Matić, Gordana, Todorović, Vera N, Paunović, Ivan R, "Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids" in Molecular Medicine, 18, no. 11 (2012):189-1465,
https://hdl.handle.net/21.15107/rcub_ibiss_1085 .