BACKGROUND: Steroid receptor-associated and regulated protein (SRARP) suppresses tumor progression and modulates steroid receptor signaling by interacting with estrogen receptors and androgen receptors in breast cancer. In endometrial cancer (EC), progesterone receptor (PR) signaling is crucial for responsiveness to progestin therapy. The aim of this study was to investigate the role of SRARP in tumor progression and PR signaling in EC. METHODS: Ribonucleic acid sequencing data from the Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium, and Gene Expression Omnibus were used to analyze the clinical significance of SRARP and its correlation with PR expression in EC. The correlation between SRARP and PR expression was validated in EC samples obtained from Peking University People's Hospital. SRARP function was investigated by lentivirus-mediated overexpression in Ishikawa and HEC-50B cells. Cell Counting Kit-8 assays, cell cycle analyses, wound healing assays, and Transwell assays were used to evaluate cell proliferation, migration, and invasion. Western blotting and quantitative real-time polymerase chain reaction were used to evaluate gene expression. The effects of SRARP on the regulation of PR signaling were determined by co-immunoprecipitation, PR response element (PRE) luciferase reporter assay, and PR downstream gene detection. RESULTS: Higher SRARP expression was significantly associated with better overall survival and disease-free survival and less aggressive EC types. SRARP overexpression suppressed growth, migration, and invasion in EC cells, increased E-cadherin expression, and decreased N-cadherin and Wnt family member 7A ( WNT7A ) expression. SRARP expression was positively correlated with PR expression in EC tissues. In SRARP -overexpressing cells, PR isoform B (PRB) was upregulated and SRARP bound to PRB. Significant increases in PRE-based luciferase activity and expression levels of PR target genes were observed in response to medroxyprogesterone acetate. CONCLUSIONS This study illustrates that SRARP exerts a tumor-suppressive effect by inhibiting the epithelial-mesenchymal transition via Wnt signaling in EC. In addition, SRARP positively modulates PR expression and interacts with PR to regulate PR downstream target genes.
Female ; Humans ; Receptors, Progesterone/metabolism* ; Proteomics ; Cell Line, Tumor ; Endometrial Neoplasms/metabolism* ; Cell Proliferation/genetics* ; Luciferases/pharmacology* ; Gene Expression Regulation, Neoplastic/genetics*

OBJECTIVES: Clarifying the expression of breast cancer receptor is the key to clinical treatment for breast cancer. This study aims to explore the correlation between X-ray and clinical characteristics of 4 molecular subtypes and their receptor types of breast cancer. METHODS: A total of 439 breast cancer patients who confirmed by pathology and performed X-ray examination were enrolled. The X-ray and clinical characteristics of 4 molecular subtypes and the expression of their receptors were analyzed. RESULTS: Luminal A type showed the highest proportion of spiculate masses, and the lowest calcification score, showing significant difference with other 3 subtypes (all CONCLUSIONS Four molecular subtypes of breast cancer and their receptor expressions are correlated with X-ray and clinical characteristics, which can provide a basis for clinical diagnosis and treatment.
Biomarkers, Tumor ; Breast Neoplasms/genetics* ; Female ; Humans ; Receptor, ErbB-2/genetics* ; Receptors, Estrogen ; Receptors, Progesterone ; X-Rays

Animals ; Autophagy/genetics* ; Cholesterol/metabolism* ; Gene Expression Regulation ; Integrases/metabolism* ; Leydig Cells/metabolism* ; Male ; Mice, Knockout ; Multienzyme Complexes/metabolism* ; Phosphoproteins/metabolism* ; Primary Cell Culture ; Progesterone Reductase/metabolism* ; RNA Splicing Factors/metabolism* ; Scavenger Receptors, Class B/metabolism* ; Sequestosome-1 Protein/metabolism* ; Signal Transduction ; Sirtuin 1/genetics* ; Sodium-Hydrogen Exchangers/metabolism* ; Steroid 17-alpha-Hydroxylase/metabolism* ; Steroid Isomerases/metabolism* ; Testosterone/genetics*

Objective To approach the discordance of estrogen receptor(ER),progesterone receptor(PR),Cerb-B2,Ki-67 index and P53 expressions between primary and regional or distant recurrent lesions in recurrent or metastatic breast cancer patients.Methods Clinical and pathological data of 56 recurrent or metastatic breast cancer patients who were treated in Peking Union Medical College Hospital from January 2001 to February 2015 were retrospectively analyzed.The changes in the expressions of ER,PR,Cerb-B2,Ki-67 index,and P53 status were analyzed.Results The hormone receptor positive rate between primary tumor and recurrent or metastatic sites decreased from 60.7% to 57.1% for ER and from 55.4% to 44.6% for PR,respectively.Changes in hormone receptor status were seen at the rate of 12.5%(7/56)and 16.1%(9/56)for ER and PR,respectively.Cerb-B2 receptor positive rate increased from 19.1% to 29.5% and the discordance rate was 9.1%(4/44).The discordance rate of Ki-67 index was 24.5%(12/49).The P53 receptor positive rate increased from 37.5% to 55.6% and the discordance rate was 13.3%(6/45).Conclusion Although the relevant rules of above changes are still controversial,these findings still have great clinical significance for making effective treatment decisions of recurrent or metastatic breast cancer.
Breast Neoplasms ; genetics ; Humans ; Ki-67 Antigen ; genetics ; Receptor, ErbB-2 ; genetics ; Receptors, Estrogen ; genetics ; Receptors, Progesterone ; genetics ; Retrospective Studies ; Tumor Suppressor Protein p53 ; genetics

To examine the expressions of epithelial cell adhesion molecule (EpCAM), vimentin and N-cadherin in breast cancer and its molecular subtypes, and to explore the correlation among them.
 Methods: The expressions of EpCAM, vimentin and N-cadherin were detected by immunohistochemistry in 835 patients with breast cancer, and their correlations with clinical pathological features and prognosis were analyzed.
 Results: The expression rates of EpCAM, vimentin and N-cadherin in the patients were 53.4%, 11.4% and 9.7% respectively, which were increased with the increase in tumor size, histological grade, lymph node size, tumor node stage of metastases classification, estrogen receptor and progesterone receptor levels (all P<0.05). The positive expression rates for EpCAM protein in luminal A, luminal B (HER2-), luminal B (HER2+), HER2 overexpression and triple-negative subtypes were 19.2%, 73.0%, 48.9%, 72.2%, and 62.1% respectively; for vimentin were 3.9%, 11.4%, 14.1%, 11.1%, and 20.5% respectively; for N-cadherin were 7.0%, 5.7%, 12.0%, 12.2% and 17.4% respectively, with statistical difference (all P<0.05). EpCAM expression was positively correlated with vimentin and N-cadherin in patients with breast cancer and triple-negative breast cancer.
 Conclusion: EpCAM is overexpressed in triple-negative subtype of breast cancer and it is associated with epithelial-mesenchymal transition markers, which might be related to breast cancer progression and metastasis.
Antigens, CD ; Biomarkers, Tumor ; Breast Neoplasms ; chemistry ; classification ; genetics ; Cadherins ; Epithelial Cell Adhesion Molecule ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Immunohistochemistry ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2 ; Receptors, Estrogen ; Receptors, Progesterone ; Triple Negative Breast Neoplasms ; Vimentin

OBJECTIVETo investigate the effect of estrogen (E2), progesterone(P4), and paclitaxel (taxol) on the growth of primary human ovarian cancer cells in vitro and the expression of Drosha.

METHODSHuman ovarian cancer cells were treated with estrogen, progesterone or in combination with paclitaxel in vitro. The inhibition rate of ovarian cancer cells was assessed by methyl thiazolyl tetrazolium (MTT) assay. Apoptosis rate and cell cycle were determined by FACS analysis. The relative abundence of Drosha expression was detected by real-time quantitative PCR (qRT-PCR) and Western blotting.

RESULTSThe inhibition rate of the estrogen group, progesterone group, paclitaxel group, E2(+)Taxol group, P4(+)Taxol group was (31.53 ± 8.21)%, (25.22 ± 15.50)%, (46.71 ± 4.25)%, (69.46 ± 3.71)%, and (47.35 ± 39.02)%, respectively, significantly higher than that of the control group (0%, P<0.05 for all). Relative to the ER (-) in ovarian cancer cells,Drosha mRNA expression level of estrogen group, progesterone group, paclitaxel group, E2(+) Taxol group,and P4(+)Taxol group was 1.62 ± 0.10,1.60 ± 0.10,1.75 ± 0.16,1.95 ± 0.20, and 1.53 ± 0.06, respectively, significantly higher than that of the control group (1.00, P<0.05 for all). Relative to the ER (+)in ovarian cancer cells,the Drosha mRNA expression level of estrogen group, progesterone group, paclitaxel group, E2(+)taxol group, and P4(+)Taxol group was 1.03 ± 0.14, 1.60 ± 0.09, 1.75 ± 0.16, 1.60 ± 0.10, 1.53 ± 0.06, respectively except estrogen group, significantly higher than that of the control group (1.00, P<0.05). Relative to the ER (-) in ovarian cancer cells, the Drosha protein expression levels of the control group, estrogen group, progesterone group, paclitaxel group, E2(+) taxol group, and P4(+) Taxol group were 0.25 ± 0.05, 0.87 ± 0.30, 0.85 ± 0.38, 1.30 ± 0.21, 1.75 ± 0.83, 1.62 ± 0.82, respectively, with a significant difference between the experimental groups and the control group (P<0.05). Relative to the ER(+)ovarian cancer cells, the Drosha protein expression levels in the estrogen group, progesterone group, paclitaxel group, E2(+) taxol group, and P4(+) taxol group, were 0.28 ± 0.16, 0.85 ± 0.38, 1.30 ± 0.21, 0.94 ± 0.18, and 1.62 ± 0.82, respectively except estrogen group, significantly higher than that of the control group (0.25 ± 0.05, P<0.05 for all).

CONCLUSIONSEstrogen and progesterone in combination with paclitaxel can inhibit the growth of human ovarian cancer cells in vitro, and affect the cell apoptosis rate. Estrogen and taxol can alter the cell cycle. Estrogen and progesterone combined with paclitaxel show tumor suppressing or sensitizing effect through upregulated Drosha expression, and are associated with the estrogen receptor expression.

Antineoplastic Agents, Phytogenic ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Apoptosis ; Cell Cycle ; Cell Growth Processes ; drug effects ; Cell Line, Tumor ; Coloring Agents ; Drug Therapy, Combination ; Estrogens ; pharmacology ; Female ; Humans ; In Vitro Techniques ; Ovarian Neoplasms ; chemistry ; drug therapy ; metabolism ; pathology ; Paclitaxel ; pharmacology ; Progesterone ; pharmacology ; RNA, Messenger ; metabolism ; Receptors, Estrogen ; metabolism ; Ribonuclease III ; genetics ; metabolism ; Tetrazolium Salts ; Thiazoles ; Up-Regulation

OBJECTIVETo investigate the effect of acupuncture on progesterone (P4) and prolactin (PRL) in rats of embryo implantation dysfunction (EID).

METHODSOn the first day of pregnancy, 72 female Wistar rats were randomly allocated into the normal group, the EID model group, the acupuncture group and the P4 group (18 in each group). The normal group was injected sesame oil, while the other three groups were given mifepristone to establish the EID model. The acupuncture group and the P4 group were given treatment of acupuncture and P4 injection, respectively. The serum of P4 and PRL were detected by radioimmunoassay, and the mRNA and protein expressions of P4 receptor (PR) and PRL receptor (PRLR) were detected using real-time polymerase chain reaction and immunohistochemical method, respectively.

RESULTSCompared with the normal group, the serum levels of P4 and PRL as well as the mRNA and protein expression levels of PR and PRLR in the EID model group were significantly lowered (P<0.01 or P<0.05). The above indices in the acupuncture group and the P4 group were significantly elevated compared with the EID model group (P<0.01 or P<0.05).

CONCLUSIONAcupuncture can promote embryo implantation effectively, which might be related to the effects of acupuncture on upregulating the P4 and PRL levels in serum and the PR and PRLR expression levels in rats.

Acupuncture Therapy ; Animals ; Embryo Implantation ; Endometrium ; metabolism ; Female ; Gene Expression Regulation ; Immunohistochemistry ; Male ; Pituitary Gland ; metabolism ; Pregnancy ; Progesterone ; blood ; Prolactin ; blood ; RNA, Messenger ; genetics ; metabolism ; Rats, Wistar ; Receptors, Progesterone ; genetics ; metabolism ; Receptors, Prolactin ; genetics ; metabolism

OBJECTIVE: To evaluate the relationship between response categories assessed by magnetic resonance imaging (MRI) or pathology and survival outcomes, and to determine whether there are prognostic differences among molecular subtypes. MATERIALS AND METHODS: We evaluated 174 patients with biopsy-confirmed invasive breast cancer who had undergone MRI before and after neoadjuvant chemotherapy, but before surgery. Pathology findings were classified as a pathologic complete response (pCR) or a non-pCR, and MRI findings were designated as a radiologic CR (rCR) or a non-rCR. We evaluated overall and subtype-specific associations between clinicopathological factors including the assessment categories and recurrence, using the Cox proportional hazards model. RESULTS: There were 41 recurrences (9 locoregional and 32 distant recurrences). There were statistically significant differences in recurrence outcomes between patients who achieved a radiologic or a pCR and patients who did not achieve a radiologic or a pCR (recurrence hazard ratio, 11.02; p = 0.018 and recurrence hazard ratio, 3.93; p = 0.022, respectively). Kaplan-Meier curves for recurrence-free survival showed that triple-negative breast cancer was the only subtype that showed significantly better outcomes in patients who achieved a CR compared to patients who did not achieve a CR by both radiologic and pathologic assessments (p = 0.004 and 0.001, respectively). A multivariate analysis found that patients who achieved a rCR and a pCR did not display significantly different recurrence outcomes (recurrence hazard ratio, 2.02; p = 0.505 and recurrence hazard ratio, 1.12; p = 0.869, respectively). CONCLUSION: Outcomes of patients who achieved a rCR were similar to those of patients who achieved a pCR. To evaluate survival difference according to molecular subtypes, a larger study is needed.
Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy/mortality/*pathology ; Female ; Humans ; Kaplan-Meier Estimate ; *Magnetic Resonance Imaging ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Remission Induction

Breast Neoplasms ; metabolism ; Female ; Humans ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Receptor, Epidermal Growth Factor ; metabolism ; Receptors, Progesterone ; metabolism

PURPOSE: Bone is the most frequent site of metastasis among breast cancer patients. We investigated prognostic factors affecting survival following bone-only metastasis in breast cancer patients. MATERIALS AND METHODS: The medical records of breast cancer patients who were treated and followed at Gangnam Severance Hospital retrospectively reviewed to identify patients with bone-only metastasis. RESULTS: The median time from the diagnosis of bone-only metastasis to the last follow-up or death was 55.2 [95% confidence interval (CI), 38.6-71.9] months. The Kaplan-Meier overall survival estimate at 10 years for all patients was 34.9%. In the multivariate Cox regression model, bisphosphonate treatment [hazard ratio=0.18; 95% CI, 0.07-0.43], estrogen receptor positivity (hazard ratio=0.51; 95% CI, 0.28-0.94), and solitary bone metastasis (hazard ratio=0.32; 95% CI, 0.14-0.72) were significantly associated with longer overall survival in the bone-only recurrence group. Among the treatment modalities, only bisphosphonate treatment was identified as a significant prognostic factor. CONCLUSION: Identifying the factors influencing breast cancer mortality after bone-only metastasis will help clarify the clinical course and improve the treatment outcome for patients with breast cancer and bone-only metastasis. Bisphosphonates, as a significant prognostic factor, warrant further investigation.
Adult ; Antineoplastic Agents/therapeutic use ; Bone Neoplasms/drug therapy/genetics/*secondary ; Breast Neoplasms/drug therapy/genetics/*pathology ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Regression Analysis ; Retrospective Studies ; Survival Analysis