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A Molteni

Publications and source records attributed to A Molteni.

At least 37 records · Page 2Linked to original sources
PubMed1997

Captopril modulates hormone receptor concentration and inhibits proliferation of human mammary ductal carcinoma cells in culture.

The present study evaluated the effect of the angiotensin converting enzyme (ACE) inhibitor captopril on estrogen (ER) and progesterone (PR) receptor concentration and on proliferation in two lines of human mammary ductal carcinoma cells in culture: T-47D (ER+/PR+) and Hs578T (ER-/PR-). The incorporation of [3H]thymidine, validated by cell count, served as an index of proliferation. Compared to control cells, T-47D cells incubated for 48 hrs in 1, 2, or 5 mM captopril (but not in 0.5 mM) exhibited a reduction in ER from 130 +/- 6 to 32 +/- 32 fmol/mg cytosolic protein, and an increase in PR from 1780 +/- 120 to 2740 +/- 400 fmol/ mg protein (p < 0.05). Western analysis confirmed these drug-induced changes in the concentration of immunoreactive receptor proteins. Captopril also induced the appearance of low but detectable PR in the Hs578T cells at concentrations as low as 50 microM. Captopril inhibited the incorporation of [3H]thymidine by both cell types during a 48 hr incubation, although Hs578T cells were 2-3 times more resistant than were T-47D cells. This cytostatic effect of captopril was not due to cytotoxicity as indicated by 51Cr release, and was not accompanied by significant changes in cell cycle distribution as determined by flow cytometry. The incorporation of [3H]uridine (RNA synthesis) and [14C]alanine (protein synthesis) also were inhibited by captopril, suggesting a general antimetabolic effect of the drug in the ductal carcinoma cells. These are novel actions of a common antihypertensive agent. In contrast, the nonthiol ACE inhibitor lisinopril, and penicillamine, a thiol compound with virtually no ACE inhibitory activity, had no effect on any of these endpoints.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Annexin I in fibrotic rat lung and cultured lung fibroblasts following irradiation.

Radiation-induced lung fibrosis is a result of collagen accumulation in the interstitium, partly due to increased collagen synthesis by fibroblasts. One feature of active collagen synthesis is increased membrane trafficking in the fibroblasts. A group of proteins called annexins is believed to play a regulatory role in membrane fusion and exocytosis. Therefore, increased annexin activity might be expected in the fibrotic lung. We tested this hypothesis by measuring annexin I levels, hydroxyproline content and ultrastructural changes in radiation-induced pulmonary fibrosis in rat. Three months after a single exposure to 30 Gy of X-rays to the right hemithorax, the right lung of the rat was atrophied and fibrotic with a concomitant increase in size of the shielded left lung. Electron micrographs revealed that the irradiated lung was ladened with interstitial collagen fibrils, with increased number of fibroblasts amongst them. Hydroxyproline concentration in the irradiated lung was nearly twice that in the sham-irradiated lung. Annexin I in the irradiated lung, on the other hand, was markedly reduced, and barely detectable on immunoblots. Since increased annexin I might precede enhanced collagen production, we also measured annexin I levels in rat lungs 3 days after 30 Gy irradiation and correlated that with hydroxyproline concentration. We found no appreciable difference in annexin I levels and hydroxyproline content between sham-irradiated and irradiated lungs at 3 days. To determine whether annexin I levels in cultured fibroblasts were altered by irradiation, we assayed annexin I in cultured rat lung fibroblasts 3 days after 0.10 Gy exposure, with concomitant measurement of 14C-proline incorporation. The annexin I level in fibroblasts irradiated with 10 Gy X-rays was 55% higher than in sham-irradiated fibroblasts. However, incorporation of 14C-proline into collagenase-sensitive macromolecules in the culture medium and extracellular matrix was not different between these two groups of cells. These data demonstrate a radiation-induced increase in immunoreactive annexin I in cultured lung fibroblasts, but fail to support the hypothesis of a positive correlation between annexin I concentration and fibrosis in irradiated rat lung.

Animals↗
PubMed1996

Captopril inhibits angiogenesis and slows the growth of experimental tumors in rats.

Captopril, an inhibitor of angiotensin converting enzyme, is widely used clinically to manage hypertension and congestive heart failure. Here captopril is shown to be an inhibitor of angiogenesis able to block neovascularization induced in the rat cornea. Captopril acted directly and specifically on capillary endothelial cells, inhibiting their chemotaxis with a biphasic dose-response curve showing an initial decrease at clinically achievable doses under 10 microM and a further slow decline in the millimolar range. Captopril inhibition of endothelial cell migration was not mediated by angiotensin converting enzyme inhibition, but was suppressed by zinc. Direct inhibition by captopril of zinc-dependent endothelial cell-derived 72-and 92-kD metalloproteinases known to be essential for angiogenesis was also seen. When used systemically on rats captopril inhibited corneal neovascularization and showed the antitumor activity expected of an inhibitor of angiogenesis, decreasing the number of mitoses present in carcinogen-induced foci of preneoplastic liver cells and slowing the growth rate of an experimental fibrosarcoma whose cells were resistant to captopril in vitro. These data define this widely used drug as a new inhibitor of neovascularization and raise the possibility that patients on long term captopril therapy may derive unexpected benefits from its antiangiogenic activities.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Injury-specific cytotoxic response of tumor cells and endothelial cells.

Cytotoxicity indicated by increased release of prelabeled 51chromium (51Cr) and lactate dehydrogenase (LDH) was studied in human prostate cancer and melanoma cells in cell culture following irradiation or exposure to several injurious substances. These changes were compared to those observed in bovine aortic endothelial cells (BAEC) subjected to identical treatments. Further, the effect of irradiation on plasminogen activator (PA) secretion from prostate cancer cells, and the effect of glycine on radiation-induced cytotoxicity in BAEC were also investigated. Radiation, lipopolysaccharide and xanthine/xanthine oxidase stimulated no release of 51Cr or LDH from tumor cells, while these treatments induced a dose- and time-related loss of those cytotoxic indicators from BAEC. Protease, elastase and Triton X-100 incited loss of 51Cr and LDH from all three cell types. Radiation, lipopolysaccharide and xanthine/xanthine oxidase have been shown to cause cell injury via a common pathogenic pathway of oxidant generation. Tumor cells appear quite resistant to oxidant stress. Cell damage precipitated by protease, elastase and Triton probably involves hydrolysis of proteins and phospholipids in the cell membrane, leading to an increased leakage of intracellular proteins such as LDH and those bound with 51Cr. Radiation caused a dose- and time-related reduction in the secretion of PA from prostate cancer cells. PA is alleged to play a role in tumor metastasis; the reduced secretion could be another beneficial effect of radiation, in addition to interruption of cell proliferation, in the impediment of tumor growth and spread. Glycine diminished cytotoxic injury of BAEC inflicted by radiation. This amino acid may prove useful in offering a degree of protection of normal tissue against radiation associated side-effects.

Animals↗
PubMed1996

Dose-response effects of radiation on the permeability of endothelial cells in culture.

Increased permeability is an early and universal response of the vasculature to radiation injury, yet the biological basis of this reaction is poorly understood. The present study determined the time course and the dose-response relationship of radiation-induced hyperpermeability in cultured bovine pulmonary artery endothelial (BPAE) cells. BPAE cells were grown to a confluent monolayer on microcarrier beads, and column chromatography methods were used to evaluate permeability to two low molecular weight compounds: sodium fluorescein (NaFlsc, mol. wt. = 342) and cyanocobalamin (B12, mol. wt. = 1355). This is a novel in vitro model to study mechanisms and modifiers of radiation-induced permeability of endothelial cells under flow conditions using nonradioactive tracers. Cell-covered beads were exposed to a single dose of 10 Gy Of 137Cs gamma rays and placed in the column, and permeability was measured every 30 min for 3 h. There was a time-dependent increase in permeability to both tracers, reaching significance by 2 h. Increased permeability was accompanied by perturbations in F-actin distribution in the BPAE cells as determined by rhodamine-phalloidin fluorescence microscopy. Neither catalase nor captopril ameliorated this hyperpermeability, but dibutyryl cAMP partially prevented it. At 3 h after 0, 1, 2, 5 and 10 Gy irradiation, permeability values of 11.8 +/- 2.1, 13.9 +/- 2.2, 20.9 +/- 3.6, 24.8 +/- 2.8 and 27.2 +/- 3.3 (10(-5) cm/s, +/- SEM), respectively, were observed using NaFlsc. The increase was significant (P < 0.05) at 2 Gy or higher. Permeability to B12 was significantly elevated after 5 or 10 Gy. These results suggest that permeability of endothelial cells to low molecular weight solutes increases within 3 h after therapeutic doses of radiation, and that cAMP ameliorates this response.

Actins↗
PubMed1996

Captopril preserves function and ultrastructure in experimental radiation nephropathy.

Captopril protects rat lung from radiation-induced pneumonitis and fibrosis and preserves function and survival in experimental radiation nephropathy. This study determined the structural benefit of captopril used preventively in radiation nephropathy. Twenty-eight Wag/RijMCW rats, divided in six groups, received 0 to 17 Gray total body irradiation followed by syngeneic bone marrow transplant. Captopril 0, 62.5, 125, 250, or 500 mg/l was given in the drinking water from the time of irradiation, and the rats were killed at 20 weeks. Using light and electron microscopy, kidneys of irradiated no-drug rats showed glomerular tuft capsular adhesions and hyalinization, focal tubular necrosis, severe interstitial fibrosis, and marked thickening and hyaline degeneration of the wall of interlobular arteries and arterioles, with intimal proliferation and periadventitial edema and inflammation. Lumens of the smaller arteries were often occluded. Significant collagen deposition was present in glomeruli, interstitium, and adventitia of interlobular arteries. Marked reduction of glomerular, tubular, vascular, and interstitial damage was seen in irradiated, captopril-treated animals, with only mild focal tubular interstitial injury and fibrosis seen. alpha smooth muscle actin-positive cells, probably myofibroblasts, were enhanced in the irradiated kidneys, and this expression was reduced in a dose-related fashion by captopril. There was also reduction in the arteriolar wall thickening, luminal occlusion, and collagen deposition in captopril-treated animals. The presence of elastin was not affected by radiation or drug treatment. Blood pressure and azotemia were lower and survival was higher in irradiated drug-treated rats compared with irradiated no-drug rats. We conclude that captopril exerts significant functional and structural protection against renal radiation injury. There was notable reduction in radiation-induced fibrosis in captopril-treated animals in this model, as in experimental lung radiation injury.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

In vitro hormonal effects of soybean isoflavones.

Isoflavones exhibit a multitude of biological effects that influence cell growth and regulation, and, thus, may have potential value in the prevention and treatment of cancer. Isoflavones are weak estrogens and can function both as estrogen agonists and antagonists depending on the hormonal milieu and the target tissue and species under investigation. Genistein, one of the two primary isoflavones in soybeans, has attracted much attention from the research community, not only because of its potential antiestrogenic effects, but because it inhibits several key enzymes thought to be involved in carcinogenesis. Although still speculative, greater dietary incorporation of soybean products, because of the high concentration of isoflavones, may be a safe and effective means of reducing cancer risk.

Animals↗
PubMed1995

Inhibitors of angiotensin-converting enzyme modulate mitosis and gene expression in pancreatic cancer cells.

The angiotensin-converting enzyme (ACE) inhibitor captopril inhibits mitosis in several cell types that contain ACE and renin activity. In the present study, we evaluated the effect of the ACE inhibitors captopril and CGS 13945 (10(-8) to 10(-2) M) on proliferation and gene expression in hamster pancreatic duct carcinoma cells in culture. These cells lack renin and ACE activity. Both ACE inhibitors produced a dose-dependent reduction in tumor cell proliferation within 24 hr. Captopril at a concentration of 0.36 mM and CGS 13945 at 150 microM decreased cellular growth rate to approximately half that of the control. Neither drug influenced the viability or the cell cycle distribution of the tumor cells. Slot blot analysis of mRNA for four genes, proliferation associated cell nuclear antigen (PCNA), K-ras, protein kinase C-beta (PKC-beta) and carbonic anhydrase II (CA II) was performed. Both ACE inhibitors increased K-ras expression by a factor of 2, and had no effect on CA II mRNA levels. Captopril also lowered PCNA by 40% and CGS 13945 lowered PKC-beta gene expression to 30% of the control level. The data demonstrate that ACE inhibitors exhibit antimitotic activity and differential gene modulation in hamster pancreatic duct carcinoma cells. The absence of renin and ACE activity in these cells suggests that the antimitotic action of captopril and CGS 13945 is independent of renin-angiotensin regulation. The growth inhibition may occur through downregulation of growth-related gene expression.

Adenocarcinoma↗
PubMed1995

Annexin I concentration, phospholipase activity and thromboxane synthesis in irradiated rat lung.

Annexin I, a member of a family of Ca(2+)-dependent phospholipid-binding proteins (PLBP), has been suggested as a regulator of prostaglandin metabolism as a result of its inhibitory effect on phospholipase A2. Synthesis of prostaglandin is increased in irradiated tissue, but the mechanism underlying this increase has not been delineated. It is conceivable that a decrease in the level of annexin I resulting in increased phospholipase activity may be responsible for the enhanced synthesis of prostaglandin. Accordingly, we measured the level of a lung 36 kDa PLBP, which possesses characteristics of annexin I, as well as the activity of phospholipase and the synthesis of thromboxane A2 (TXA2) in irradiated rat lung. The right lung of rats was irradiated with 0, 15 or 30 Gy of X rays and the animals were sacrificed after 3 months. Phospholipid binding protein was assayed by its ability to transfer unilamellar liposomes to multilamellar liposomes and by immunoblotting against anti-36 kDa rabbit PLBP antisera. Production of TXA2 by minced lung tissue was determined by radioimmunoassay of its stable metabolite TXB2. Phospholipase activity was assayed by hydrolysis of [14C]dioleoylphosphatidylcholine. Our results showed that PLBP activity in the lungs irradiated with 30 Gy was lower than that in the lungs irradiated with 0 and 15 Gy (8.82 +/- 0.47 compared to 9.73 +/- 0.49 and 9.95 +/- 0.78 nmol phospholipid transferred/mg protein, respectively). Western blotting demonstrated a near total depletion of annexin I in the lungs irradiated with 30 Gy. Phospholipase activity was also lower in the lungs irradiated with 30 Gy compared to that in the lungs irradiated with 0 Gy (0.23 +/- 0.01 vs 0.32 +/- 0.01 nmol phosphatidylcholine liberated/mg protein/min, P < 0.001). Reduced phospholipase activity was observed not only in the cytosolic or soluble fraction of lung homogenate, but also in precipitates obtained after 21,000g and 100,000g centrifugation. Despite this decline in phospholipase activity, there was a 2.8-fold increase in the synthesis of thromboxane (367 +/- 65 compared to 1076 +/- 143 pg TXB2/mg tissue/10 min for lungs irradiated with 0 and 30 Gy, respectively). These results are not consistent with the hypothesis that increased synthesis of thromboxane A2 in irradiated rat lung is a direct result of elevated phospholipase activity. In fact, phospholipase activity is decreased in the irradiated lung, despite a decline in the concentration of annexin I, its putative inhibitor.

Animals↗
PubMed1994

Estrogen and progesterone receptor concordance between primary and recurrent breast cancer.

Estrogen and progesterone receptor status in breast cancer can determine therapeutic options and may provide prognostic information. The purpose of this study is to compare the concordance of the primary breast cancer steroid hormone receptor status to that of the recurrent breast cancer and to determine whether the type of second lesion (local recurrence, second primary, or metastatic lesion) and adjuvant therapy received changed the receptor concordance. The records of eighty-three patients with estrogen receptor (ER) analysis available for primary (p) and recurrent (r) breast cancer for 1976-1990 were reviewed. In addition, 32 of these patients also had available progesterone receptor (PR) values for primary and recurrent breast cancers. Statistical evaluation was performed by chi-square, Student's t-test, and Wilcoxon signed-rank test. ER concordance (primary/recurrent, p/r) was identified in 59/83 (71%) patients; PR concordance was identified in 18/32 (56%) patients. Whether the second lesion was a local recurrence, second primary, or a metastatic lesion did not affect ER concordance or PR concordance. Adjuvant chemotherapy, hormonal therapy, or radiation therapy, either alone or in combination, did not affect ER or PR concordance. The disease-free survival (DFS) for patients with ER (p+)/(r-) (primary receptor positive/recurrent receptor negative) was significantly shorter than those with ER (p-)/(r+)(27.6 +/- 7.4 months versus 50.6 +/- 7.6 mo, P = 0.04). The DFS for PR (p+)/(r-) patients was 28.8 +/- 7.9 months compared to the DFS of 46.8 +/- 11.8 months for PR (p-)/(r+) patients (P = NS). A significantly shorter DFS for ER (p+)/(r-) patients compared to ER (p-)/(r+) patients and a trend towards a shorter DFS for PR (p+)/(r-) patients compared to PR (p-)/(r+) patients may reflect a loss of hormonal regulation or an increase in cancer aggressiveness.

Breast Neoplasms↗
PubMed1994

Captopril inhibits proliferation of human lung fibroblasts in culture: a potential antifibrotic mechanism.

The angiotensin converting enzyme (ACE) inhibitor captopril, a free-thiol compound used widely as an antihypertensive agent, also inhibits radiation-induced pulmonary fibrosis in rats (Ward et al., Int J Radiat Oncol Biol Phys 19:1405, 1990). In an attempt to clarify the antifibrotic mechanism of captopril in vivo, the present study examined the effect of the drug on proliferation of human lung fibroblasts in culture. Captopril produced a drug dose-dependent reduction in fibroblast proliferation and 3H-thymidine incorporation during a 24-72-hr incubation. This cytostatic action of captopril was not the result of cytotoxicity as assessed by trypan blue exclusion, or by 51Cr or lactate dehydrogenase (LDH) release. Fibroblasts stimulated to proliferate by basic FGF were more sensitive to the antimitotic effect of captopril than were unstimulated cells. The ability of captopril to inhibit 3H-thymidine incorporation was not reversed by exogenous angiotensin 2, and was not mimicked by the nonthiol ACE inhibitor lisinopril. These data indicate that the cytostatic effect of captopril was not attributable to ACE inhibition. Penicillamine, a thiol compound with virtually no ACE inhibitory activity, also reduced fibroblast 3H-thymidine incorporation, indicating that the antimitotic action of captopril may represent a nonspecific sulfhydryl effect. This study suggests that the antifibrotic activity of captopril in irradiated lung may result in part from a direct inhibition of fibroblast proliferation, particularly in fibroblasts responding to mitogenic stimuli.

Angiotensin II↗
PubMed1992

Radiation pneumotoxicity in rats: modification by inhibitors of angiotensin converting enzyme.

The present study determined whether inhibitors of angiotensin converting enzyme (ACE) can ameliorate radiation-induced pulmonary endothelial dysfunction and pulmonary fibrosis in rats sacrificed 2 months after a range of single doses of 60Co gamma rays to the right hemithorax. Four indices of pulmonary endothelial function were monitored: right lung ACE and plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Hydroxyproline (HP) content served as an index of pulmonary fibrosis. Rats consumed either control powdered chow or feed containing one of five modifying agents continuously after irradiation. The modifiers included three ACE inhibitors: Captopril, CL242817, and CGS13945, respectively, a thiol, a thioacetate, and a nonthiol compound. All of the ACE inhibitors are analogues of proline. Two additional modifiers were tested: penicillamine, a thiol with no ACE inhibitory activity; and pentoxifylline, a vasodilator that is neither a thiol nor an ACE inhibitor. Radiation produced a dose-dependent decrease in lung ACE and PLA activity, and an increase in PGI2 and TXA2 production and in HP content. All ACE inhibitors attenuated the radiation-induced suppression in lung ACE and PLA activity. All thiol or thioacetate compounds ameliorated the radiation-induced increase in PGI2, TXA2, and HP. The two agents that were both thiols and ACE inhibitors (Captopril and CL242817) spared all of the radiation reactions, while the compound that was neither a thiol nor an ACE inhibitor (pentoxifylline) spared none of the reactions. These data suggest a novel application for ACE inhibitors in general, and for Captopril in particular, as modifiers of radiation pneumotoxicity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Response to head-up tilt in cramping and noncramping hemodialysis patients.

Hemodialysis-associated skeletal muscle cramps are generally ascribed to a reduction in plasma volume, but during this procedure, it is not known how volume contraction results in cramps. To elucidate this mechanism, we compared responses to one hour of 60 degrees head-up tilt in 8 patients who cramped during no more than one-sixth of their dialyses and in 8 patients who cramped at least half the time. Age and recumbent blood pressure were similar in each group, but more patients with frequent cramps had diabetes underlying their renal failure (p = 0.013) and had been dialyzed for less than 3 years (p = 0.020). Baseline plasma renin activity and plasma norepinephrine and arginine vasopressin concentrations were similar in both groups, except plasma renin activity in one patient with frequent cramps, which was 15 times higher than in the other patients. After tilting, systolic blood pressure fell an average of 17% in patients who cramped infrequently (p = 0.0031) but only 10% in frequently cramping patients. The ratio of tilt/recumbent norepinephrine levels exceeded 1.5 in 7 patients with frequent cramps but was less than this in 6 patients who cramped infrequently (p = 0.020). One of the 2 infrequently cramping patients with a ratio above 1.5 was the only individual to have a normal renin response to tilt. We propose that cramps are prone to occur during hemodialysis in patients whose sympathetic nervous system response to volume stress is partially intact but is not modulated by concurrent activation of the renin-angiotensin system.

Adult↗
PubMed1992

Pentoxifylline does not spare acute radiation reactions in rat lung and skin.

Male rats were exposed to single doses (0-30 Gy) of 60Co gamma rays to the right hemithorax. Half of each dose group consumed only control powdered chow after irradiation, and half consumed feed containing 0.10% (w/w) pentoxifylline (50 mg/kg/day). The severity of epilation and desquamation in the field of the radiation port was scored weekly. Two months after irradiation the animals were killed, and pulmonary endothelial function was monitored by the activity of lung angiotensin converting enzyme (ACE) and plasminogen activator (PLA), and by production of prostacyclin (PGI2) and thromboxane (TXA2). The amount of hydroxyproline (HP) in the lung served as an index of pulmonary fibrosis. Radiation produced a dose-dependent decrease in ACE and PLA activity in the right lung and an increase in the production of PGI2 and TXA2. This endothelial dysfunction was accompanied by an increase in wet weight and in protein and HP content in the irradiated lung. Pentoxifylline spared only the increase in lung wet weight and protein content, and actually elevated the radiation-induced hyperproduction of PGI2 and TXA2. The severity of the epilation and desquamation reactions increased with increasing radiation dose and time but was independent of diet. These data indicate that pentoxifylline, despite some promising pharmacological actions, has no beneficial effect on acute radiation reactions in rat lung and skin.

Administration, Oral↗
PubMed1991

High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura.

The purpose of this study was to estimate the incidence and to establish which factors were associated with an increased risk of hemorrhagic complications in an historic cohort of 117 consecutive and unselected patients with chronic idiopathic thrombocytopenic purpura (ITP). Sixty-eight patients (58%) underwent medical treatment and/or splenectomy and 33 (48% of treated) achieved a complete stable remission. At equivalent platelet count the incidence of major hemorrhagic complications was significantly higher in aged (greater than 60 years) than in younger (less than 40 years) patients (10.4% v 0.4%/pt-y, relative risk = 28.9, P less than .01). A previous hemorrhagic event was identified as another major risk factor for hemorrhage (relative risk = 27.5, P less than .0005), while hypertension and underlying disorders had no influence. We conclude that age more than 60 years and a previous history of bleeding are major risk factors for severe hemorrhages in adults with ITP.

Adult↗
PubMed1991

Stable expression of the human estrogen receptor in HeLa cells by infection: effect of estrogen on cell proliferation and c-myc expression.

We have introduced the human estrogen receptor (ER) gene into HeLa cells, a human adenocarcinoma cell line of uterine origin, by infection. The ER cDNA was inserted into a retroviral vector (pMV7-ER) which also contains the neomycin resistance gene to allow for selection of stable infected clones. Northern analysis showed exogenous ER expression in stable clones. The ER protein expressed was about 66 kDa, similar to native MCF-7 ER, and binds with high affinity to estrogen (E2). We have also observed that addition of E2 at 10(-8) M inhibits the growth of the I-1 clone which expresses high levels of the ER (223 fmol/mg cytosol protein). The inhibitory effects of E2 directly correlate with the quantity of ER in the cells. E2-induced gene expression analysis showed that pS2 and progesterone receptor (PgR), genes induced in MCF-7 cells by E2, are not induced in the ER+ HeLa clones. However, c-myc expression was found to be decreased and may be responsible for the observed growth inhibition by E2.

Breast Neoplasms↗
PubMed1990

Sex steroid hormone receptors in normal and dysplastic bone disorders in children.

Children with monostotic and polyostotic bone dysplasias often exhibit localized bone overgrowth. We investigated the presence of nuclear estrogen and nuclear progesterone receptors by solid-phase radioimmunoassay, immunocytochemistry, and radioligand binding in osteoblast cell cultures derived from the areas of overgrowth of membranous bone, noninvolved membranous bone, and normal membranous bone from children undergoing elective craniotomy. Membranous bone of normal children had demonstrable levels of nuclear estrogen and progesterone receptors identified by radioimmunoassay and immunocytochemical assay. Two- to threefold increased levels of these receptors (p less than 0.001 versus normals) were found in cultures derived from the involved bone of two children with monostotic fibrous dysplasia and in one patient with polyostotic dysplasia (McCune-Albright syndrome). The noninvolved bone in our patients with fibrous dysplasia exhibited nuclear sex steroid hormone receptor levels similar to those in the normal children. Radioligand binding studies demonstrated increased sex steroid hormone receptors in cultures derived from involved osteoblasts. The presence of an increased level of sex steroid hormone receptor was accompanied by increased alkaline phosphatase activity and increased production of osteocalcin in vitro compared to normal or noninvolved bone. The mechanisms by which sex steroid hormone receptor levels are increased in the ostotic dysplasias remain to be established.

Alkaline Phosphatase↗