Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biologic properties of breast cancer in men that might reflect alterations in pathogenesis from the disease in women were examined. We studied 22 tumors from males, 18 invasive carcinomas, three of which were papillary, and three in situ tumors of which one was papillary, and one papilloma. Our data support the previously reported high incidence of papillary carcinoma in men. Estrogen receptor status and the expression of cancer-associated antigens recognized by antibodies DF3, B73.2, SP-1, and c-erbB-2 were compared to matched tumors from females. Immunocytochemistry was performed on formalin-fixed, paraffin-embedded sections using standard avidin-biotin techniques; anti-PSA was used to exclude the possibility of metatastic prostate cancer, and 12 cases of gynecomastia were included as nonmalignant controls. The incidence of estrogen receptor positivity was higher in tumors from males (73%) than from females (54%), as has been reported previously. The range of expression of all breast cancer antigens tested in male tumors was similar to that observed in females, but some interesting differences were noted. With the exception of the anti-mucin DF3, all the antibodies reacted only with neoplastic tissues. Expression of the oncoprotein c-erbB-2 was lower (17%) in males than in females (33%), despite the preponderance in men of the large-cell type carcinomas that have been associated with c-erbB-2 expression. Unexpectedly, the pregnancy-associated hormone detected by SP-1 was expressed in 33% of tumors from males and, in contrast to females, was found in less differentiated tumors.
 ...
PMID:Immunocytochemical characterization of male breast cancer. 136 97

The expression of the estrogen-regulated breast-cancer-associated pS2 gene was examined in 75 stomach resections taken from 45 patients. The 600-base pS2 mRNA was found in all of the 47 non-neoplastic samples at varying levels: in the histologically normal group we observed a Poisson-type distribution, whereas 79% of the tissues exhibiting dysplastic features expressed high levels of transcript. Tumour samples expressed relatively lower pS2 mRNA, with only 18% having high levels and 43% with no detectable expression. These differences were not correlated to tumour grading, stage or site. No amplification or rearrangement of the pS2 gene was found. Immunohistochemical analysis of formalin-fixed paraffin sections, using a polyclonal antibody against pS2 protein, showed specific staining of both cytoplasm and membrane of epithelial cells in the neck region of antral and body glands as well as in luminal secretions. Immunoreactivity was observed in the sub-nuclear region of foveolar cells, with specialized gland and goblet cells in atrophic gastritis being negative. Heterogeneous but strong focal cytoplasmic staining was seen in tumour cells as well as in dysplastic epithelium. Two gastric cell lines, KATO III and MKN-45, derived from poorly differentiated adenocarcinomas also expressed pS2, whereas 3 other lines from well differentiated parental tumours did not. Genomic analysis revealed a BamHI polymorphism in Kato III cells and in the non-expressing MKN-28 cells. Immunostaining to pS2 protein was also demonstrated in the cytoplasm of KATO III cells, but neither these nor any of 30 tissues examined showed any positivity with a monoclonal antibody (MAb) to estrogen receptor. Our results suggest that pS2 is normally expressed in human stomach, possibly in association with secretory activity, and becomes down-regulated during malignancy.
 ...
PMID:Expression of the pS2 gene in normal, benign and neoplastic human stomach. 258 60

A detailed retrospective analysis was undertaken of the effect of perioperative blood transfusion on long-term survival of 113 patients with Dukes' Stages A, B and C1 cancer of the colon and 383 patients with invasive cancer of the breast who were treated in our institution between 1973 and 1978 and followed for 5 to 10 years. In the patients with colon cancer, a significant adverse effect of transfusion on long-term survival was seen. In this group there was a cumulative 5-year overall survival of 48% for the transfused and 74% for the nontransfused patients (P = 0.007, log-rank test). Perioperative blood transfusion was associated with a relative risk of 3.42 for all deaths (P = 0.005) and 4.25 for death due to cancer (P = 0.03), after adjustment for other important variables such as age, sex, stage, location of tumor, surgical procedure, and preoperative hemoglobin level. In contrast, in our study group of patients with breast cancers, who all underwent a modified radical mastectomy, no effect of blood transfusion on long-term survival was seen. Multivariate analysis adjusting for size of tumor, number of positive regional lymph nodes, menopausal status, estrogen receptor status and the addition or absence of chemotherapy, did not show any increased risk in all deaths or death due to cancer associated with blood transfusion. Although no definite explanation is available, our data show that there seems to be a difference in the relationship between perioperative blood transfusion and survival for colon and breast cancer patients.
 ...
PMID:Perioperative blood transfusion and cancer prognosis. Different effects of blood transfusion on prognosis of colon and breast cancer patients. 380 42

In this study, the anti-promoting effect of voluntary (wheel) exercise on 7, 12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumorigenesis was investigated. All rats were fed high fat diets (23% of calories as fat) to mimice the typical western diet. Two doses of DMBA were used to determine if the antipromoting effects of exercise were dependent on the strength of the initiating agent. In addition, tumor estrogen receptors were assayed to determined whether exercise, through an estrogen-suppressing mechanism, selects for estrogen receptor-negative tumors. Female Sprague-Dawley rats were fed a semi-purified 23% fat (corn oil) diet (AIN-76A) and, on day 50 of age administered DMBA by gavage at 5 or 10 mg/rat. Rats were then randomized into 4 groups (n = 30) as follows: 1) low DMBA/sedentary; 2) low DMBA/exercise; 3) high DMBA/-sedentary; and 4) high DMBA/exercise. Active rats were placed in wheel-cage units, which allowed voluntary access to an activity wheel for 133 (low DMBA) and 77 (high DMBA) days, respectively, Sedentary rats were placed in conventional cages. Both active groups exhibited significantly lower total tumor numbers than their sedentary controls: 75 vs 102 (low DMBA) (p < 0.05) and 90 vs 160 (high DMBA) (p < 0.001). Compared to sedentary controls, latency was significantly lengthened in the low but not the high DMBA active groups; multiplicity, in contrast, was significantly decreased in the high, but not the low DMBA exercised group. Exercise had no effect on overall tumor incidence. When segregated into exercise tertiles, total tumor active compared to the least active tertile, particularly in the high DMBA group.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inhibition of rat mammary tumorigenesis by voluntary exercise. 836 66

The role of the a form of estrogen receptor (ER alpha) gene expression in the regulation of testosterone-dependent male reproductive behaviors was investigated using ER knockout mice (ERKO), which are specifically deficient in functional ER alpha, but not ER beta, gene expression. Previous studies in gonadally intact ERKO mice revealed that male aggressive behavior was greatly reduced by the lack of a functional ER alpha gene. In the present study the almost complete suppression of male-typical offensive attacks was further confirmed in ERKO mice that had been singly housed since weaning. Regarding aggression, it was also found that ER alpha gene disruption virtually abolished the propensity to initiate offensive attacks, even though ERKO mice could elicit attacks from resident C57BL/6J mice as wild-type (WT) and heterozygous littermates. Daily injection of testosterone propionate (TP) was completely ineffective in inducing aggressive behavior in gonadectomized ERKO mice, whereas it successfully restored aggression in WT mice. In contrast, male sexual behaviors, mounts and intromissions, were induced by daily injection of TP in both gonadectomized ERKO and WT mice. In addition to TP, dihydrotestosterone propionate (DHTP) was also effective in restoring mounts in ERKO mice, although DHTP was much more potent in WT mice than in ERKO mice. Neither TP nor DHTP, however, ever induced ejaculation in ERKO mice. These results together with previous findings in gonadally intact ERKO mice suggest that ER alpha may be responsible for the regulation by testosterone of consummatory, but not motivational, aspects of male sexual behavior. Finally, ERKO male mice retrieved newborn pups placed in their home cage with similar latencies to males of the two other genotypes. During parental behavior tests, however, a higher percentage of ERKO mice (70%) showed infanticide compared with WT mice (35%). The latter result was interpreted as showing that ER alpha activation by testosterone during the perinatal period may exert a suppressive effect on testosterone-inducible infanticide in adulthood. With respect to three major testosterone-dependent behavioral systems reflecting masculinization, these findings demonstrate three different types of effects due to ER alpha gene disruption.
 ...
PMID:Modifications of testosterone-dependent behaviors by estrogen receptor-alpha gene disruption in male mice. 983 45

The role of gene expression of the estrogen receptor-alpha form (ER alpha) in the regulation of female reproductive behavior was investigated in estrogen receptor knockout (ERKO) mice, deficient specifically for the ER alpha, but not the ER beta, gene. Estrogen- or estrogen- plus progesterone-treated gonadectomized ERKO mice did not show any lordosis response. Detailed behavioral analysis revealed that ERKO females were also deficient in sexual behavioral interactions preceding the lordosis response. They were extremely rejective toward attempted mounts by stud male mice, which could not show any intromissions. During resident-intruder aggression tests, gonadally intact ERKO females were more aggressive toward female intruder mice than wild-type (WT) mice. Gonadectomy did not influence the levels of aggressive behavior, and their genotype differences when mice were tested both before and after gonadectomy. However, when mice were tested after gonadectomy for the first time, very few ERKO mice showed aggression. In contrast to aggression, male-type sexual behavior shown by resident mice toward female intruder mice during aggression tests was not different between ERKO and WT mice and was completely abolished after gonadectomy of the resident mice. Finally, it was also found that ERKO females showed greatly reduced levels of parental behavior toward newborn pups placed in their home cage. These changes in parental behavior were not influenced by gonadectomy. ERKO females retrieved significantly fewer numbers of pups with longer latencies compared with wild-type (WT) or heterozygous (HZ) littermates when they were tested as gonadally intact or 20-65 days after gonadectomy. In addition, during parental behavior tests, a significantly higher percentage of ERKO mice exhibited infanticide compared with WT and HZ mice, which rarely showed infanticide. Taken together, these findings suggest that ER alpha gene expression plays a key role in female mice, not only for sexual behavior but also for other interrelated behaviors, such as parental and aggressive behaviors. In addition, persistence of genotype differences in parental and aggressive behavior after gonadectomy indicates that ER alpha activation during neural developmental processes may also be involved in the regulation of these behaviors.
 ...
PMID:Roles of estrogen receptor-alpha gene expression in reproduction-related behaviors in female mice. 983 46

Invasive breast carcinomas are characterized by a complex pattern of chromosomal alterations. We applied comparative genomic hybridization (CGH) to analyze 105 primary breast carcinomas using histograms to indicate the incidence of DNA imbalances of tumor subgroups and difference histograms to compare invasive ductal carcinomas (IDC) with lobular carcinomas (ILC), well and poorly differentiated carcinomas (G1/G3) and estrogen receptor-positive and -negative tumors (ER(+)/ER(-)). Only single imbalances showed a higher incidence in ILC compared with IDC, i.e., gains on chromosomes 4 and 5q13-q23 as well as deletions on chromosomes 6q, 11q14-qter, 12p12-pter, 16q, 17p, 18q, 19, and 22q. Of these, particularly gains of 4 and losses at 16q21-q23, and 18q12-q21 were statistically significant. For most loci, IDC showed more alterations providing a genetic correlate to the fact that ductal carcinoma overall is associated with a worse prognosis than ILC. Of these, many imbalances showing statistical significance were also observed in G3 and ER(-) tumors, i.e., deletions at 2q35-q37, 3p12-p14, 4p15-p16, 5q, 7p15, 8p22-p23, 10q, 11p, 14q21-q31, 15q, and gains at 2p, 3q21-qter, 6p, 8q21-qter, 10p, 18p11-q11, and 20q, suggesting that they contribute to a more aggressive tumor phenotype. By contrast, gains on chromosome 5q13-q23 as well as deletions at 6q, 16q and 22q were more prevalent in G1 and ER(+) tumors. The ratio profiles of all cases as well as histograms are accessible at our CGH online tumor database at http://amba.charite.de/cgh. Our results highlight distinct chromosomal subregions for cancer-associated genes. In addition, these imbalances may serve as markers for a genetic classification of invasive breast cancer.
 ...
PMID:Patterns of chromosomal imbalances in invasive breast cancer. 1086 9

Central catecholaminergic systems play an important role in the control of reproductive activities including sexual behavior, luteinizing hormone (LH) and prolactin secretion. It has been reported that catecholaminergic neurons in the locus coeruleus (A6) are activated by mating in rabbits and ferrets, animals known as reflex ovulators. This study used Fos as a marker of neuronal activity to examine whether brainstem catecholaminergic neurons are activated by mating in the spontaneous ovulator, the female rat. Proestrous rats receiving intromissions (mated group) from males or mounts-without-intromission (mounted group) were sacrificed along with rats taken directly from their home cage (control group) 90 min after the beginning of mating or mounting. Double-label immunocytochemistry was used to examine the expression of c-Fos in catecholaminergic neurons labeled by tyrosine hydroxylase (TH) antibody, or adrenergic neurons labeled by phenylethanolamine-N-methyl transferase (PNMT) antibody. Double label immunofluorescent immunohistochemistry was used to determine the number of neurons containing the estrogen receptor (ERalpha) that were activated by mating in these brain areas. The results showed that mating-with-intromissions induced a significant increase in the percentage of TH/Fos colabeled neurons in both A1 and A2 cells compared to mounting-without-intromission or control. In both these areas, over 50% ERalpha-ir neurons were activated after mating while mounting-without-intromission did not affect the percentage of colabeled Fos/ERalpha neurons. In A6 region, neither the expression of Fos nor the percentage of TH/Fos colabeled cells was influenced by either mating or mounting compared to controls. The percentage of PNMT-containing neurons colabeled with Fos was not different in C1 and C2 among the three experimental groups. The results indicate that catecholaminergic neurons were activated by mating in A1 and A2 but not in adjoining adrenergic C1 and C2 cells. In contrast to the findings that catecholaminergic neurons in A6 are activated by mating in induced ovulators, mating did not affect neuronal activity in A6 neurons in the female rat. In A1 and A2 areas, a high percentage of neurons containing ERalpha were activated by mating suggesting both tactile and hormonal information may converge on these populations of neurons. The activated catecholaminergic neurons in A1 and A2 may be an important pathway by which sensory information generated during sexual interaction modulates both behavior and pituitary function.
 ...
PMID:Mating-activated brainstem catecholaminergic neurons in the female rat. 1125 Nov 89

GRP78 is a stress-inducible chaperone protein with antiapoptotic properties that is overexpressed in transformed cells and cells under glucose starvation, acidosis, and hypoxic conditions that persist in poorly vascularized tumors. Previously we demonstrated that the Grp78 promoter is able to eradicate tumors using murine cells in immunocompetent models by driving expression of the HSV-tk suicide gene. Here, through the use of positron emission tomography (PET) imaging, we provide direct evidence of spontaneous in vivo activation of the HSV-tk suicide gene driven by the Grp78 promoter in growing tumors and its activation by photodynamic therapy (PDT) in a controlled manner. In this report, we evaluated whether this promoter can be applied to human cancer therapy. We observed that the Grp78 promoter, in the context of a retroviral vector, was highly activated by stress and PDT in three different types of human breast carcinomas independent of estrogen receptor and p53. Complete regression of sizable human tumors was observed after prodrug ganciclovir treatment of the xenografts in immunodeficient mice. In addition, the Grp78 promoter-driven suicide gene is strongly expressed in a variety of human tumors, including human osteosarcoma. In contrast, the activity of the murine leukemia virus (MuLV) long-terminal repeat (LTR) promoter varied greatly in different human breast carcinoma cell lines, and in some cases, stress resulted in partial suppression of the LTR promoter activity. In transgenic mouse models, the Grp78 promoter-driven transgene is largely quiescent in major adult organs but highly active in cancer cells and cancer-associated macrophages, which can diffuse to tumor necrotic sites devoid of vascular supply and facilitate cell-based therapy. Thus, transcriptional control through the use of the Grp78 promoter offers multiple novel approaches for human cancer gene therapy.
 ...
PMID:Spontaneous and controllable activation of suicide gene expression driven by the stress-inducible grp78 promoter resulting in eradication of sizable human tumors. 1521 14

Overexpression of the lipogenic enzyme fatty acid synthase (FAS) is a common molecular feature in subsets of sex-steroid-related tumors including breast carcinomas that is associated with poor prognosis. In this study, we explored whether breast-cancer associated FAS (oncogenic antigen-519) is regulated by the progestin component in oral contraceptives. In addition, we examined the role of FAS hyperactivity on progestin-regulated breast cancer cell proliferation, survival and metastatic properties. We found that in estrogen receptor (ER)- and progesterone receptor (PR)-positive MCF-7 human breast cancer cells, synthetic progestins used in oral contraceptives including norethynodrel (NOR) and norethindrone, induced a dose-dependent increase of FAS enzymatic activity, with a maximum response (> or = 4-fold) occurring at a concentration of 10(-8) M. FAS activity was only slightly stimulated after exposure to two other progestins, medroxy-progesterone acetate (MPA) and megestrol acetate (MGA), which are used in postmenopausal hormone replacement therapy and high-dose progestin treatment therapy. Western blot analyses showed that NOR-induced stimulation of FAS activity correlated closely with NOR-induced up-regulation of FAS protein expression. To determine the role of FAS accumulation following NOR exposure, we pharmacologically examined the requirement for FAS activity in NOR-stimulated breast cancer cell proliferation and survival. The novel small compound C75 (a slow-binding FAS inhibitor) blocked NOR-induced breast cancer cell proliferation in anchorage-dependent assays. More importantly, pharmacological inhibition of FAS activity completely abolished NOR-stimulated soft-agar colony formation of MCF-7 cells. To evaluate the involvement of PR and ER signalings in NOR-induced up-regulation of FAS expression and activity, NOR was used in combination with either the anti-progestin RU486 (mifepristone) or the pure antiestrogen ICI 182,780 (Faslodex). RU486 and ICI 182,780 similarly abolished NOR-induced FAS activation, supporting the notion that PR- and ER-mediated FAS up-regulation might play different roles in NOR-stimulated breast cancer cells. Interestingly, when we evaluated the involvement of PR and ER signalings on NOR-induced breast cancer cell proliferation, the anti-estrogen ICI 182,780, but not the anti-progestin RU486, was found to inhibit NOR-stimulated proliferation and survival of MCF-7 cells in anchorage-dependent and -independent assays. To further determine whether NOR produced their effects via the ER, we evaluated its effects on endogenous ER transcriptional activity by using transient transfection assays with an estrogen-response element reporter construct (ERE-Luciferase). In the absence of E2 stimulation, treatment with NOR dramatically increased the levels of ERE-dependent transcriptional activity. This estrogenic like-effect of NOR was blocked by the addition of ICI 182,780, whereas RU486 failed to inhibit NOR-induced ERE activity. In summary, this study provides direct evidence that: a) a number of synthetic progestins used in oral contraceptives significantly activates breast cancer-associated FAS (OA-519) activity and expression in hormone-dependent breast cancer cells; b) FAS activity is necessary for progestin-induced anchorage-independent growth and survival of human breast cancer cells, and c) activation of ER, but not PR signaling, is the stimulatory mechanism through which synthetic progestins enhance a FAS-dependent proliferative and pro-survival signaling. These findings should be helpful to explain the conflicting evidence linking oral contraceptives and breast cancer risk through the estrogenic activation of tumor-associated FAS (OA-519), a molecular marker associated with poor clinical outcome of breast cancer disease.
 ...
PMID:The estrogenic activity of synthetic progestins used in oral contraceptives enhances fatty acid synthase-dependent breast cancer cell proliferation and survival. 1587 Aug 63


1 2 3 4 5 6 7 8 9 Next >>