Characterization of Heterogeneous Prostate Tumors in Targeted Pten Knockout Mice

Previously, we generated a preclinical mouse prostate tumor model based on PSA-Cre driven inactivation of Pten. In this model homogeneous hyperplastic prostates (4-5m) developed at older age (>10m) into tumors. Here, we describe the molecular and histological characterization of the tumors in order to better understand the processes that are associated with prostate tumorigenesis in this targeted mouse Pten knockout model. The morphologies of the tumors that developed were very heterogeneous. Different histopathological growth patterns could be identified, including intraductal carcinoma (IDC), adenocarcinoma and undifferentiated carcinoma, all strongly positive for the epithelial cell marker Cytokeratin (CK), and carcinosarcomas, which were negative for CK. IDC pattern was already detected in prostates of 7–8 month old mice, indicating that it could be a precursor stage. At more than 10 months IDC and carcinosarcoma were most frequently observed. Gene expression profiling discriminated essentially two molecular subtypes, denoted tumor class 1 (TC1) and tumor class 2 (TC2). TC1 tumors were characterized by high expression of epithelial markers like Cytokeratin 8 and E-Cadherin whereas TC2 tumors showed high expression of mesenchyme/stroma markers such as Snail and Fibronectin. These molecular subtypes corresponded with histological growth patterns: where TC1 tumors mainly represented adenocarcinoma / intraductal carcinoma, in TC2 tumors carcinosarcoma was the dominant growth pattern. Further molecular characterization of the prostate tumors revealed an increased expression of genes associated with the inflammatory response. Moreover, functional markers for senescence, proliferation, angiogenesis and apoptosis were higher expressed in tumors compared to hyperplasia. The highest expression of proliferation and angiogenesis markers was detected in TC2 tumors. Our data clearly showed that in the genetically well-defined PSA-Cre;Pten-loxP/loxP prostate tumor model, histopathological, molecular and biological heterogeneity occurred during later stages of tumor development.     

New potential regulators of uterine leiomyomata from DNA arrays: the ionotropic glutamate receptor GluR2

In the post-Genome era, new concepts emerge about the growth regulation of uterine leiomyomata. Screening of leiomyoma and myometrial tissues with DNA arrays revealed numerous genes up-regulated in leiomyomata that were not known to be expressed in the human uterus. GluR2, a subunit of a ligand-gated cation channel, is up-regulated in leiomyomata relative to myometrium by 15- to 30-fold at the protein and mRNA level and is localized in endothelial cells. GluR2 pre-mRNA in leiomyoma and myometrial tissues is nearly 100% edited at the Q/R site, indicative of low Ca(2+) permeability of the ion channels. In spontaneous leiomyomata in women or leiomyomata induced in the guinea pig model, there is a likely synergism linking increased production of estradiol and all-trans retinoic acid with up-regulation of nuclear receptor PPARgamma and RXRalpha proteins to support tumor growth. GluR2 might be coupled to this synergism directly or via interleukin-17B, kinesin KIF5 or related genes also up-regulated in leiomyomata. GluR antagonists should be tested as inhibitors of leiomyoma growth.     

Molecular Pathway Analysis Indicates a Distinct Metabolic Phenotype in Women With Right-Sided Colon Cancer

Colon cancer is the third most commonly diagnosed cancer in the United States. Recent reports have shown that the location of the primary tumor is of clinical importance. Patients with right-sided colon cancers (RCCs) (tumors arising between the cecum and proximal transverse colon) have poorer clinical outcomes than those with left-sided colon cancers (LCCs) (tumors arising between the distal transverse colon and sigmoid colon, excluding the rectum). Interestingly, women have a lower incidence of colon cancer than men, but have a higher propensity for RCC. The reason for this difference is not known; however, identification of sex-specific differences in gene expression by tumor anatomical location in the colon could provide further insight. Moreover, it could reveal important predictive markers for response to various treatments. This study provides a comprehensive bioinformatic analysis of various genes and molecular pathways that correlated with sex and anatomical location of colon cancers using four publicly available annotated data sets housed in the National Center for Biotechnology Information's Gene Expression Omnibus. We identified differentially expressed genes in tumor tissues from women with RCC, which showed attenuated energy and nutrient metabolism when compared with women with LCC. Specifically, we showed the downregulation of 5′ AMP-activated protein kinase alpha subunit (AMPKα) and anti-tumor immune responses in women with RCC. This difference was not seen when comparing tumor tissues from men with RCC to men with LCC. Therefore, women with RCC may have a specific metabolic and immune phenotype which accounts for differences in prognosis and treatment response.     

The endothelin axis in uterine leiomyomas: new insights

The endothelin axis, comprising endothelin-1 (ET-1) and its receptors (ETA and ETB), is involved in the pathophysiology of different human tumors. Here we review conventional approaches and gene expression profiling indicating the association of ET-1 and its cognate receptors with human and rat leiomyomas, the most common benign tumors of myometrium. Specifically, ET-1/ETA interactions affect human and rat leiomyoma cell proliferation through protein kinase C and mitogen-activated protein kinase-dependent signaling pathways. Recent experiments demonstrate that the ET-1 axis exerts a potent antiapoptotic effect involving sphingolipid metabolism and prostaglandin-endoperoxide synthase 2/prostaglandin system in the rat Eker leiomyoma tumor-derived ELT3 cell line. Evidence supports that steroid hormones, growth factors, and extracellular matrix are key regulators of the leiomyoma growth. Interestingly, the ET-1 axis is under steroid hormones and can cooperate with these growth factors. Therefore, ET-1 alone or in association with these factors could contribute to the complex regulation of uterine tumor growth, such as proliferation, survival, and extracellular matrix production. This review summarizes current knowledge and emerging data on ET-1 in uterine leiomyoma pathology.     

Weight-Related Attitudes and Behaviors of Women Who Diet to Lose Weight: A Comparison of Black Dieters and White Dieters

Obesity is a significant health problem among black women in the United States. Black women are two to three times more likely than white women to be obese. The present study sought to examine race differences in attitudes and beliefs about dieting, motivations underlying dieting efforts, and actual dieting strategies and behaviors. To achieve this aim, a subset of female survey respondents (n = 324) was drawn from a pool of more than 20,000 subscribers to Consumer Reports. All survey respondents had made at least one dieting effort within 3 years of the time of the study. For this study, we used all black female respondents (n = 162) and a matched sample (i.e., matched on age, educational attainment, and personal income) of white women (n = 162). Black women did weigh significantly more than Caucasian women, therefore, BMI was used as a covariate in all subsequent analyses. Black and white women were significantly different in a number of domains. Compared to white women, black women experienced less social pressure about their weight, initiated dieting later in life, and were significantly less likely to diet at each developmental milestone. However, the two groups of women did not differ in reasons for undertaking their most recent dieting efforts, or in the types of weight loss strategies they had employed. Nor were there differences between the black and white women in methods for coping responses with dietary relapse or in rates of disordered eating. These findings are discussed in terms of their implications for both treatment and prevention of obesity in black women.     

Phosphorylation of PTEN (phosphatase and tensin homologue deleted on chromosome ten) protein is enhanced in human fibromyomatous uteri

PTEN phosphatase, a product of PTEN tumor suppressor gene, exists in cells in phosphorylated and unphosphorylated form and has a central role in regulation of PI3K/Akt signalling which is involved in non-genomic action of estradiol. The purpose of this study was to analyze the level of total PTEN and phosphoPTEN parallel to phosphoAkt in leiomyoma and adjacent myometrium during menstrual cycle and at menopause. The expression of total PTEN in leiomyoma and myometrium did not change throughout the experiments. However, the level of phosphoPTEN was increased in leiomyoma during menstrual cycle. The phosphorylation of PTEN in myometrium was lower during secretory phase than that of proliferative phase. The phosphoAkt was abundant in leiomyoma, and its expression was higher during menstrual cycle than in myometrium. The phosphorylation of PTEN was directly related to phosphoAkt, suggesting a direct link between the inactivation of PTEN and activation of Akt. At the decline of sexual steroids, at menopause, no differences were observed in the expression of studied proteins between the two types of tissues. Our results suggest that the altered phosphorylation of PTEN protein and the consequent activation of survival signals may contribute to the pathomechanism of leiomyoma.     

Genome-wide DNA methylation indicates silencing of tumor suppressor genes in uterine leiomyoma

Background

Uterine leiomyomas, or fibroids, represent the most common benign tumor of the female reproductive tract. Fibroids become symptomatic in 30% of all women and up to 70% of African American women of reproductive age. Epigenetic dysregulation of individual genes has been demonstrated in leiomyoma cells; however, the in vivo genome-wide distribution of such epigenetic abnormalities remains unknown.

Principal Findings

We characterized and compared genome-wide DNA methylation and mRNA expression profiles in uterine leiomyoma and matched adjacent normal myometrial tissues from 18 African American women. We found 55 genes with differential promoter methylation and concominant differences in mRNA expression in uterine leiomyoma versus normal myometrium. Eighty percent of the identified genes showed an inverse relationship between DNA methylation status and mRNA expression in uterine leiomyoma tissues, and the majority of genes (62%) displayed hypermethylation associated with gene silencing. We selected three genes, the known tumor suppressors KLF11, DLEC1, and KRT19 and verified promoter hypermethylation, mRNA repression and protein expression using bisulfite sequencing, real-time PCR and western blot. Incubation of primary leiomyoma smooth muscle cells with a DNA methyltransferase inhibitor restored KLF11, DLEC1 and KRT19 mRNA levels.

Conclusions

These results suggest a possible functional role of promoter DNA methylation-mediated gene silencing in the pathogenesis of uterine leiomyoma in African American women.     

Metastasizing and Non-Metastasizing Tumors Likely Evolve from DNA Phenotypes via Independent Pathways

We have recently discovered, using statistical models of Fourier transform-infrared spectra, two distinct cancer DNA phenotypes in histologically normal tissues surrounding non-metastasizing primary tumors and tumors with evidence of distant metastases. Structural comparisons of the DNA from these tumor types imply that each evolves via a separate pathway from DNA phenotypes originating in progenitor cells. These findings challenge the widely-held concept of metastasis.     

Matrix production and remodeling as therapeutic targets for uterine leiomyoma

Uterine leiomyoma, commonly known as fibroids, is a benign neoplasm of smooth muscle in women. The incidence of clinically symptomatic fibroids in reproductive-age women is approximately 20 %, with nearly 80 % of black women suffering from this condition. Symptoms include severe pain and hemorrhage; fibroids are also a major cause of infertility or sub-fertility in women. Uterine leiomyoma consist of hyperplastic smooth muscle cells and an excess deposition of extracellular matrix, specifically collagen, fibronectin, and sulfated proteoglycans. Extracellular matrix components interact and signal through integrin-β1 on the surface of uterine leiomyoma smooth muscle cells, provide growth factor storage, and act as co-receptors for growth factor-receptor binding. ECM and growth factor signaling through integrin-β1 and growth factor receptors significantly increases cell proliferation and ECM deposition in uterine leiomyoma. Growth factors TGF-β, IGF, PDGF, FGF and EGF are all shown to promote uterine leiomyoma progression and signal through multiple pathways to increase the expression of genes encoding matrix or matrix-modifying proteins. Decreasing integrin expression, reducing growth factor action and inhibiting ECM action on uterine leiomyoma smooth muscle cells are important opportunities to treat uterine leiomyoma without use of the current surgical procedures. Both natural compounds and chemicals are shown to decrease fibrosis and uterine leiomyoma progression, but further analysis is needed to make inroads in treating this common women’s health issue.     

Maternal Obesity and Breast‐feeding Practices Among White and Black Women

Despite the increase in obesity among women of reproductive ages, few studies have considered maternal obesity as a risk factor for breast‐feeding success. We tested the hypothesis that women who are obese (BMI = 30–34.9) and very obese (BMI ≥35) before pregnancy are less likely to initiate and maintain breast‐feeding than are their normal‐weight counterparts (BMI = 18.5–24.9) among white and black women. Data from 2000 to 2005 South Carolina Pregnancy Risk Assessment Monitoring System (PRAMS) were used. The overall response rate was 71.0%; there were 3,517 white and 2,846 black respondents. Black women were less likely to initiate breast‐feeding and breast‐fed their babies for a shorter duration than white women. Compared to normal‐weight white women, very obese white women were less likely to initiate breast‐feeding (odds ratio: 0.63; 95% confidence interval (CI) = 0.42, 0.94) and more likely to discontinue breast‐feeding within the first 6 months (hazard ratio (HR) = 1.89; 95% CI: 1.39, 2.58). Among black women, prepregnancy BMI was neither associated with breast‐feeding initiation nor with breast‐feeding continuation within the first 6 months. Because very obese white women are less likely to initiate or continue breast‐feeding than other white women, health professionals should be aware that very obese white women need additional breast‐feeding support. Lower rates of breast‐feeding among black women suggest that they should continue to be the focus of the programs and policies aimed at breast‐feeding promotion in the United States.     

Effects of progesterone on uterine leiomyoma growth and apoptosis

Uterine leiomyomas appear during the reproductive years and regress after menopause, indicating the ovarian steroid-dependent growth potential. Recently we have found that the use of levonorgestrel-releasing intrauterine system (IUS) is effective in the long-term contraception and management of menorrhagic women with uterine myomas because of a striking reduction in menorrhagia. These clinical experiences prompted us to characterize the effects of progestin on the proliferation and apoptosis of leiomyoma cells cultured in vitro. As epidermal growth factor (EGF) has been shown to mediate estrogen action and play a crucial role in regulating leiomyoma growth, we also investigated the effects of sex steroids on EGF and EGF receptor (EGF-R) expression in leiomyoma cells. In cultures of leiomyoma cells, the addition of either E(2) (10 ng/ml) or P(4) (100 ng/ml) resulted in an increase in proliferating cell nuclear antigen (PCNA) expression in the cells; whereas in cultures of normal myometrial cells, the addition of E(2) augmented PCNA expression in the cells, but P(4) did not. Immunoblot analysis revealed that leiomyoma cells contained immunoreactive EGF and that P(4) treatment resulted in an increase in EGF expression in the cells. In contrast, E(2) treatment augmented EGF-R expression in cultured leiomyoma cells, but P(4) did not. These results indicate that P(4) up-regulates the expression of PCNA and EGF in leiomyoma cells, whereas E(2) up-regulates the expression of PCNA and EGF-R in those cells. It is, therefore, conceivable that P(4) and E(2) act in combination to stimulate the proliferative potential of leiomyoma cells through the induction of EGF and EGF-R expression. We also found that Bcl-2 protein, an apoptosis-inhibiting gene product, was abundantly expressed in leiomyoma relative to that in normal myometrium, suggesting that the abundant expression of Bcl-2 protein in leiomyoma cells may be one of the molecular bases for the enhanced growth of leiomyoma relative to that of normal myometrium in the uterus. Furthermore, Bcl-2 protein expression in leiomyoma cells was up-regulated by P(4), but down-regulated by E(2). Therefore, it seems likely that P(4) may also participate in leiomyoma growth through the induction of Bcl-2 protein in leiomyoma cells.     

Using AI-Based Evolutionary Algorithms to Elucidate Adult Brain Tumor (Glioma) Etiology Associated with IDH1 for Therapeutic Target Identification

Adult brain tumors (glioma) represent a cancer of unmet need where standard-of-care is non-curative; thus, new therapies are urgently needed. It is unclear whether isocitrate dehydrogenases (IDH1/2) when not mutated have any role in gliomagenesis or tumor growth. Nevertheless, IDH1 is overexpressed in glioblastoma (GBM), which could impact upon cellular metabolism and epigenetic reprogramming. This study characterizes IDH1 expression and associated genes and pathways. A novel biomarker discovery pipeline using artificial intelligence (evolutionary algorithms) was employed to analyze IDH-wildtype adult gliomas from the TCGA LGG-GBM cohort. Ninety genes whose expression correlated with IDH1 expression were identified from: (1) All gliomas, (2) primary GBM, and (3) recurrent GBM tumors. Genes were overrepresented in ubiquitin-mediated proteolysis, focal adhesion, mTOR signaling, and pyruvate metabolism pathways. Other non-enriched pathways included O-glycan biosynthesis, notch signaling, and signaling regulating stem cell pluripotency (PCGF3). Potential prognostic (TSPYL2, JAKMIP1, CIT, TMTC1) and two diagnostic (MINK1, PLEKHM3) biomarkers were downregulated in GBM. Their gene expression and methylation were negatively and positively correlated with IDH1 expression, respectively. Two diagnostic biomarkers (BZW1, RCF2) showed the opposite trend. Prognostic genes were not impacted by high frequencies of molecular alterations and only one (TMTC1) could be validated in another cohort. Genes with mechanistic links to IDH1 were involved in brain neuronal development, cell proliferation, cytokinesis, and O-mannosylation as well as tumor suppression and anaplerosis. Results highlight metabolic vulnerabilities and therapeutic targets for use in future clinical trials.     

Impairment of adenylate cyclase activity and G-proteins in human uterine leiomyoma

The mechanisms responsible for the growth of uterine leiomyoma (a frequent cause of infertility in women) are largely unknown. Some data supports that cAMP plays a role in the growth of uterine cells but there are no reports on the status of the cAMP producing system in this human benign neoplasia. In this study, biopsies from leiomyoma and the adjacent myometrium were taken from menstruating women subjected to total hysterectomy for leiomyoma. Adenylate cyclase activity was determined by a protein-binding method, and the expression of alpha(s), alphai1/2, alphai3 and alphai0) G-protein subunits was analysed by immunoblot. The leiomyoma samples exhibited a decreased expression of as and ai1/2 with respect to the adjacent myometrial tissue. No differences were observed in alphai3 and alphaio protein expression. The basal adenylate cyclase activity as well as the efficacy (as assessed by the maximal stimulation levels) of either forskolin or, to a lesser extent, Gpp[NH]p on stimulation the enzyme activity was significantly lower in leiomyoma than in myometrium, whereas the potency (as assessed by the ED50 values) of these two agents did not vary. Present data indicate that the human leiomyoma is associated with low levels of cAMP. It is conceivable that the loss of sensitivity of adenylate cyclase to endogenous regulatory molecules could be related to the pathogenesis of human leiomyomas given that cAMP inhibits the MAP-kinase cascade in uterine tissues.     

角蛋白与肿瘤

角蛋白属于I型和II型中间纤维,是上皮细胞中间纤维的主要组成蛋白。角蛋白对上皮细胞及组织的稳定性和完整性具有重要的功能,此外,许多角蛋白还参与细胞内的信号转导通路。角蛋白的基因突变会导致一系列的遗传性皮肤病,还能引起肝脏、口腔粘膜、食管、外阴、直肠粘膜的白海绵痣等疾病。最近大量研究发现,角蛋白在人类多种类型肿瘤中也存在特异性表达,角蛋白及其抗体在肿瘤的免疫化学诊断、核转移、精确的分型或分类等方面具有重要的作用,并且还有助于预测肿瘤治疗反应和预后情况。因此,研究角蛋白与肿瘤之间的相互联系,揭示它们的作用机制对肿瘤的诊断和治疗有着重要意义。该文回顾了近年来角蛋白的分子生物学研究概况及临床应用,对各种角蛋白与肿瘤发生、进展、诊断以及预后的关系进行综述,同时对存在的问题及困难作了探讨并对未来的研究进行了展望。     

角蛋白与肿瘤

角蛋白属于I型和II型中间纤维,是上皮细胞中间纤维的主要组成蛋白。角蛋白对上皮细胞及组织的稳定性和完整性具有重要的功能,此外,许多角蛋白还参与细胞内的信号转导通路。角蛋白的基因突变会导致一系列的遗传性皮肤病,还能引起肝脏、口腔粘膜、食管、外阴、直肠粘膜的白海绵痣等疾病。最近大量研究发现,角蛋白在人类多种类型肿瘤中也存在特异性表达,角蛋白及其抗体在肿瘤的免疫化学诊断、核转移、精确的分型或分类等方面具有重要的作用,并且还有助于预测肿瘤治疗反应和预后情况。因此,研究角蛋白与肿瘤之间的相互联系,揭示它们的作用机制对肿瘤的诊断和治疗有着重要意义。该文回顾了近年来角蛋白的分子生物学研究概况及临床应用,对各种角蛋白与肿瘤发生、进展、诊断以及预后的关系进行综述,同时对存在的问题及困难作了探讨并对未来的研究进行了展望。     

Black and White Women in Maryland Receive Different Treatment for Cervical Cancer

Purpose

Despite an overall decrease in incidence, the death rate from cervical cancer in the United States remains higher in black women than their white counterparts. We examined the Maryland Cancer Registry (MCR) to determine treatment factors that may explain differences in outcomes between races in the state of Maryland.

Methods

Incident cervical cancers in the MCR 1992–2008 were examined. Demographics, tumor characteristics and treatments were compared between races and over time.

Results

Our analysis included 2034 (1301 white, 733 black) patients. Black women were more likely to have locally advanced or metastatic disease at diagnosis (p<0.01). They were more likely to receive any radiation or chemotherapy combined with radiation and less likely to receive surgery (p<0.01). When adjusted for stage and insurance status black women had 1.50 (95% CI 1.20–1.87) times the odds of receiving radiation and 1.43 (95% CI 1.11–1.82) times the odds of receiving chemotherapy. Black women with cervical cancer had 0.51 times the adjusted odds (95% CI 0.41–0.65) of receiving surgery compared to white women. Racial differences in treatment did not change significantly over time.

Conclusions

Surgical treatment for newly diagnosed cervical cancer in the state of Maryland was significantly less common amongst black women than white during our study period. Equivalent treatments are not being administered to white and black patients with cervical cancer in Maryland. Differences in care may contribute to racial disparities in outcomes for women with cervical cancer.     

Adipocyte coculture induces a pro-inflammatory,fibrotic, angiogenic,and proliferative microenvironment in uterine leiomyoma cells

ObjectiveObesity and its consequences are among the biggest challenges facing the healthcare system. Uterine leiomyomas are the most common gynecologic tumors. The risk of leiomyoma increases with obesity, but the underlying mechanisms of this association remain unclear. The aim of the present study to determine the cellular and molecular mechanisms by which adipocyte contributes to both leiomyoma tumor initiation and promotion.MethodsPrimary myometrium and leiomyoma cells were isolated from patients who underwent a hysterectomy or myomectomy. Pro-inflammatory, fibrotic, and angiogenic factors were measured using a multiplex cytokine array in human primary and immortalized myometrial and leiomyoma cells cocultured with human adipocyte (SW872) cells, or in animal ELT3 leiomyoma cells cocultured with 3 T3-L1 adipocytes. The free fatty acids (FFAs) and fatty acid-binding protein 4 (FABP4) levels were measured using immunofluorescence assays. Other protein abundances were determined using western blots. The expression levels of TNF-α, MCP-1, phospho-NF-κB, TGFβ3 and VEGF-A in lean and obese in different leiomyoma patients were determined by immunofluorescence staining.ResultsAdipocytes promote inflammation, fibrosis, and angiogenesis in uterine leiomyoma cells by upregulating associated factors, such as IL-1β, TNF-α, MCP-1, GM-CSF, TGF-βs, PLGF, VEGF, HB-EGF, G-CSF and FGF2. Coculture led to the transfer of FFAs and FABP4 from adipocytes to leiomyoma cells, suggesting that adipocytes may modulate metabolic activity in these tumor cells. Increased levels of FFA and FABP4 expressions were detected in obese leiomyoma tissue compared to lean. The adipocyte–leiomyoma cell interaction increased the phospho-NF-κB level, which plays a key role in inflammation, restructuring metabolic pathways, and angiogenesis. Obese leiomyoma patients expressed a higher amount of TNF-α, MCP-1, phospho-NF-κB, TGFβ3 and VEGF-A than lean leiomyoma patients, consistent with in vitro findings. Furthermore, we found that adipocyte secretory factors enhance leiomyoma cell proliferation by increasing PCNA abundance. Finally, the inhibition of the inflammatory factors TNF-α, MCP-1, and NF-κB abrogated the adipocyte coculture-induced proliferation of leiomyoma cells.ConclusionsAdipocytes release inflammatory, fibrotic, and angiogenic factors, along with FFAs, which contribute to a tumor-friendly microenvironment that may promote leiomyoma growth and can represent a new target for leiomyoma prevention and treatment.     

间隙连接蛋白基因connexin43、ER、PR的表达在子宫平滑肌瘤中相关性研究

研究细胞间隙连接蛋白基因43（connexin43,CX43）及其蛋白、雌激素受体（estrogen receptor,ER）、孕激素受体（progesterone receptor,PR）在子宫平滑肌瘤中的表达,从核酸及蛋白水平探讨在子宫平滑肌瘤发生中的相关关系。应用核酸原位杂交技术和SP免疫组织化学法,研究37例子宫平滑肌瘤、20例正常子宫平滑肌组织中cx43mRNA及其蛋白、ER、PR的表达规律。结果显示,cx43mRNA及其蛋白、ER、PR在子宫平滑肌瘤中的表达明显高于在子宫平滑肌组织中的水平,差异有显著性（P＜0.05）。cx43mRNA及其蛋白在子宫平滑肌瘤中的过度表达,是子宫平滑肌瘤发生过程的重要事件,与ER、PR水平升高呈现一致性,对进一步揭示子宫平滑肌瘤的复杂分子机制、寻求可靠的早期标志有重要意义。