• Asian-Australasian Journal of Animal Sciences
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• v.16 no.9
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• pp.1261-1267
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• 2003

We have investigated whether HspBP1, a Hsp70 binding protein, could have effect on the assembly of the bovine progesterone receptor (bPR) with a chaperone complex consisting of bovine Hsp90 (bHsp90), bovine Hsp70 (bHsp70), Hop, Ydj-1, and p23. The bPR, isolated in its native conformation, loses its function to interact with progesterone hormone in the absence of this protein complex. However, in the presence of bHsp90, bHsp70, Hop, p23 and Ydj-1, its function could be restored in vitro. Our findings here indicate that the inclusion of HspBP1 to five-protein system prevented the proper assembly of progesterone receptor-chaperone complex and induce the loss of bPR ability to interact with hormone. Immunoprecipitation assays of bPR with HspBP1 show that the presence of HspBP1 did not have any effect on the assembly of Ydj-1 and bHsp70 with the progesterone receptor. However, further assembly of Hsp90, Hop and p23 was completely prevented and the function of the bPR was lost. In vitro competition and protein folding assays indicated that the binding of HspBP1 to bHsp70 prevented the ternary complex formation of bHsp70, bHsp90, and Hop. These results indicate that HspBP1 is a negative regulator of the assembly of Hsp90, Hop and Hsp70, and thus, prevent the proper maturation of unliganded bPR with chaperones assembly system.

• Journal of Animal Science and Technology
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• v.59 no.5
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• pp.12.1-12.7
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• 2017

Background: Despite the widespread use of dexamethasone in veterinary and human medicine, it is reported to cause some severe pregnancy related side effects like abortion in some animals. The mechanism of the response is not clear but seems to be related to interspecies and/or breed difference in response which may involve alterations in the concentrations of some reproductive hormones. Methods: Twenty Sahel goats comprising 18 does and 2 bucks were used for this study. Pregnancies were achieved by natural mating after synchronization. Repeated dexamethasone injections were given at 0.25 mg/kg body weight. Blood samples were collected biweekly for hormonal assay. Uterine biopsies were harvested at days 28 and day 78 of gestation through caesarean section for immunohistochemical analysis using 3 pregnant does randomly selected from each group at each instant. Data were expressed as Means ${\pm}$ Standard Deviations and analyzed using statistical soft ware package, GraphPad Instant, version 3.0 (2003) and progesterone receptor (PR) were scored semi-quantitatively. Results: Dexamethasone treatments had no significant (p > 0.05) effect on progesterone and estrogen concentrations in pregnant Sahel goats but up regulated PR from 2+ to 3+ in second trimester. Conclusion: As dexamethasone adverse effect on placenta is an established fact, the lack of effect on progesterone level in this study may be due to the fact that unlike other species whose progesterone production during pregnancy is placenta - dependent, in goats is corpus luteum - dependent. Consequently dexamethasone adverse effect on placenta reported in literatures did not influence progesterone levels during pregnancy in Sahel goat. The up regulation of progesterone receptor (PR) in Sahel goat gravid uterus is a beneficial effects and that dexamethasone can safely be used in corpus luteum - dependent progesterone secreting pregnant animal species like Sahel goat and camel. Therefore source of progesterone secretions during pregnancy should be considered in clinical application of dexamethasone in pregnancy.

• Development and Reproduction
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• v.27 no.4
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• pp.195-203
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• 2023

Exposure to environmental chemicals, including endocrine-disrupting chemicals, during the gestational period can have profound adverse effects on several organs in offspring. Bisphenol A (BPA) can infiltrate the human body through food and drinks, and its metabolites can cross both the placental and the blood-brain barriers. In this study, we investigate the effect of gestational exposure to BPA on epigenetic, biochemical, and histological modifications in the uterine tissues of F1 adult offspring rats. Pregnant rats were exposed to BPA from gestational day 8-15, and changes in global DNA methylation in uterine tissues obtained from adult offspring born to the exposed mothers were analyzed. Global DNA methylation analysis revealed that gestational exposure to BPA resulted in DNA hypomethylation in the uterus. Progesterone receptor (PR) protein expression in uterine tissues was monitored using western blot analysis, which revealed that the PR protein content was considerably higher in all BPA-exposed groups than in the control. Immunohistochemical examination for the PR revealed that intense PR-positive cells were more frequently observed in the BPA-exposed group than in the control group. To date, the evidence that the upregulation of PRs observed in the present study was caused by the non-methylation of specific PR promoter regions is lacking. Conclusively, these results indicate that exposure to BPA during gestation induces epigenetic alterations in the uteri of adult female offspring. We speculate that the global DNA hypomethylation and upregulation of the PR observed simultaneously in this study might be associated with the uterus.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5047-5052
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• 2012

Introduction: Breast cancer is the most common malignancy of women in Kashmir. This study was conducted with the objective of assessing hormone receptor positivity and its correlation with age at diagnosis, tumor size, histological grade and lymph node metastasis. Materials and Methods: 132 newly diagnosed cases of invasive breast cancer diagnosed at the Department of Pathology, SKIMS, Srinagar, J&K, were included after excluding biopsies, in-situ lesions and recurrence cases. Results: Mean age of the patients was 48.2 years, 59.1% being ${\leq}50$ years of age. Mean duration of symptoms was 6.32 months. Most lesions (65.1%) were 2-5 cm and 16.7% were ${\geq}5.0$ cm in greatest dimension. The predominant (80.3%) morphology was IDC-NOS. The majority of the cases presented as grade II (52.1%) lesions and lymph node involvement was present in 65.2%. ER and PR were positive in 66.3% and 63.4% cases, respectively, increasing with rising age. High grade lesions and larger size tumors were more likely to be ER and PR negative. No correlation was found between ER/PR status and lymph node metastasis. Conclusions: ER and PR expression in breast cancers in the current study was found to be higher than studies done in India/Asia but lower than studies conducted in the West, even on Indian/Asian immigrants. Markedly lower receptor expression in Indian/Asian studies is likely due to preanalytic variables, thresholds for positivity, and interpretation criteria. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer are strongly advocated for standardization of receptor evaluation and for clinical management of breast cancer patients to provide best therapeutic options.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7839-7842
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• 2014

Background: Breast cancer is the most common malignancy in women worldwide and the second most common cancer in females in India. Receptor status may be important for survival. Objective: To analyse and correlate the clinical and morphological parameters with receptor status in breast carcinoma patients in a tertiary care institution in Southern India. Materials and Methods: This retrospective study involved 320 patients of breast cancer diagnosed in an oncology hospital over a period of $3^{1/2}$ years. Data was analysed using SPSS Version 21. Results: Some 60.6% patients with breast carcinomas belonged to the age group of 40 to 60 years. The most common histological type was infiltrating ductal carcinoma, not otherwise specified, accounting for 84.4% of patients. On immunohistochemistry, estrogen receptor (ER) and progesterone receptor (PR) were expressed in 56.3% and 53.1% of cases, respectively. Conclusions: Breast cancers in India, a developing country, occur in younger women and tend to be more aggressive with lower rates of ER and PR expression and higher histological tumor grades. Both ER and PR status of the tumors had significant associations with the patient age, pathological TNM stage and histological tumor grade.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3363-3367
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• 2016

Background: Breast cancer (BC) is a major health issue worldwide as well as in Pakistan. All women belonging to any race, ethnicity or lineage are in danger of developing breast cancer. Significant factors influencing the development of breast malignancies are the genetic background, environmental conditions, reproductive parameters, the consequences of female hormones both intrinsic and extrinsic, alteration of immune status, and biologic determinants. Materials and Methods: Overall 150 biopsy proven patients were included in the study. Samples were submitted for histopathology and determination of estrogen and progesterone receptor expression and HER-2/neu status. Associations with other characteristics like age, tumor stage, node involvement, histological grade were also studied. Results: Mean age at presentation was 46.7 years. The majority had invasive ductal carcinoma, 100 (84.7%), and were in stage pT3, 54 (45.7%). Important relationships (P<0.05) were found among ER, PR positivity, and Her 2 neu overexpression. However, no noteworthy link was identified amongst ER, PR, Her 2 neu and tumor grade, stage, age, lymph node involvement except for the menopausal status. Conclusions: In summary, breast cancer patients featured an advanced stage of disease, more lymph node involvement, and moderately high grade tumors and with more estrogen, progesterone receptor and HER-2 positive tumors.

• Korean Journal of Clinical Laboratory Science
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• v.36 no.2
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• pp.185-192
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• 2004

Overexpressions of the estrogen receptors(ER), progesterone receptors(PR) and C-erbB-2 protein are important determiners of the response to chemotherapy in the breast cancer. For detecting ER, PR and C-erbB-2, immunohistochemistry are currently regarded as standard method. The purposes of this study compared to histologic grade and expression of the ER, PR and C-erbB-2 in breast cancer. We examined overexpression of ER, PR and C-erbB-2 protein in 84 breast carcinomas by using immunohistochemical stains. The following results were obtained. For histologic grade, 10 cases(11.9%) showed carcinoma in situ, 16 cases(19%) showed grade I, 36 cases (42.9%) showed grade II, and 22 cases(26.2%) showed grade III among the 84 test samples. The average positive rate ER and PR was 63%, 46% showed carcinoma in situ, 80%, 60% showed grade I, 64%, 41% showed grade II, 34%, 23% showed grade III, respectively. The induction of PR increased when induction of ER increased, thus showing significant relationship(p<0.05). The expression of C-erbB-2 protein was 9 cases(10.7%) in one positive(1+), 9 cases(10.7%) in two positive(2+), and 9 cases(10.7%) in three positive(3+). C-erbB-2 protein expression showed no statistical significance. In conclusion, ER and PR positive rates were inversely associated with histologic grades significantly(p<0.05). C-erbB-2 showed no significant difference with histologic grade. However ER, PR and C-erbB-2 showed significant relationship with each other(p<0.05). Therefore, these findings might be an important prognostic factor and might be arranged as a regular pathological examination in cases of breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9233-9239
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• 2014

Background: We aimed to evaluate the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression discordance in matched pairs of primary breast cancer and lymph node metastasis specimens and determine the effect of discordance on prognosis. Materials and Methods: Among all patients diagnosed with lymph node metastases from 2004 to 2007, primary tumors and paired lymph node metastases were resected from 209 patients. The status of ER, PR, and HER2 expression was analyzed immunohistochemically in 200, 194, and 193 patients, respectively. Discordance was correlated with prognosis. Results: Biomarker discordance between primary tumors and paired lymph node metastases was 25.0% (50/200) for ER status, 28.9% (56/194) for PR status, and 14.0% (27/193) for HER2 status. ER positivity was a significant independent predictor of improved survival when analyzed in primary tumors and lymph node metastases. Patients with PR-positive primary tumors and paired lymph node metastases displayed significantly enhanced survival compared to patients with PR-positive primary tumors and PR-negative lymph node metastases. Patients with ER- and PR-positive primary tumors and paired lymph node metastases who received endocrine therapy after surgery displayed significantly better survival than those not receiving endocrine therapy. Similalry treated patients with PR-negative primary tumors and PR-positive paired lymph node metastases also displayed better survival than those not receiving endocrine therapy. Conclusions: Biomarker discordance was observed in matched pairs of primary tumors and lymph node metastases. Such cases displayed poor survival. Thus, it is important to reassess receptor biomarkers used for lymph node metastases.

• Investigative Magnetic Resonance Imaging
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• v.19 no.3
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• pp.137-145
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• 2015

Purpose: To investigate correlations of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type 2 (HER2) statuses with magnetic resonance imaging (MRI) features and clinicohistological characteristics in patients with invasive lobular carcinoma (ILC). Materials and Methods: Data from 64 histologically confirmed ILCs were analyzed retrospectively. Preoperative breast MRI was reviewed for morphology and dynamic contrast-enhanced kinetics of the tumor. Pathologic reports were reviewed for ER, PR, and HER2 positivity, tumor size, lymph node metastasis, and the number of metastatic lymph nodes. Furthermore, there was an investigation of the MRI features and clinicohistologic characteristics, according to the ER, PR, and HER2 statuses. Results: A significant difference in MRI features and clinicohistological tumor characteristics were observed only in relation to PR status. Of the 64 ILCs, 10 (15.6%) were PR negative. PR negative cancers, compared with PR positive cancers, were more likely to present as non-mass enhancement (P = 0.027); have a significantly larger mean tumor size ($5.00{\pm}1.05cm$ vs. $2.57{\pm}0.21cm$, P = 0.021); and have significantly more metastatic lymph nodes (P = 0.010). Conclusion: PR negative ILC presented more frequently as non-mass enhancement on MRI, with larger tumors and increased numbers of metastatic lymph nodes. Therefore, the PR status plays an important role in determining MRI features and clinicohistological characteristics of ILC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2427-2431
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• 2014

Triple-negative breast cancers (TNBC), characterized by absence of the estrogen receptor (ER) and progesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2), have a poor prognosis. To overcome therapy limitations of TNBC, various new approaches are needed. This mini-review focuses on discovery of new targets and drugs which might offer new hope for TNBC patients.