PubMed Health⌕ Search

Biomedical subjects

Y K Fung

Publications and source records attributed to Y K Fung.

At least 19 recordsLinked to original sources
PubMed2006

Functional outcome of the hand following flexor tendon repair at the 'no man's land'.

PURPOSE: To evaluate the functional outcome of the hand following flexor tendon repair at 'no man's land' using 2 strands of a modified Kessler core suture and combined controlled motion rehabilitation protocol. METHODS: Records of 31 zone-2 flexor tendon injuries in 21 digits of 16 patients between July 2000 and June 2005 were reviewed retrospectively. The injured tendons were repaired within 24 hours using 2 strands of a modified Kessler core suture, reinforced by a continuous circumferential epitendon suture. All patients completed a rehabilitation protocol that included active extension against a rubber band, passive flexion, and controlled passive extension and passive flexion exercises. Functional outcome of the fingers was assessed using the Buck-Gramcko II score. Hand grip strength, rehabilitation period, and rupture rate were also measured. RESULTS: 17 (81%) out of 21 digits in 15 out of 16 patients achieved an excellent-to-good functional grade. The remaining patient with concomitant injuries to 4 (19%) digits attained a poor functional grade, attributable to poor compliance with the rehabilitation protocol. The mean rehabilitation period was 130 days and the mean grip strength was 78% that of the uninjured side. Concomitant digital nerve injury did not adversely affect the final outcome. Only one (4.8%) patient experienced a rupture. CONCLUSION: The surgical method and rehabilitation protocol used for zone-2 flexor tendon injury is safe and results in a reasonably good functional outcome.

Adolescent↗
PubMed2003

Effects of nicotine on bone mass and strength in aged female rats.

This study investigated the effects of nicotine on bone mass and biomechanical properties in aged, estrogen-replete (sham-operated) and estrogen-deplete (ovariectomized) female rats. Eight month old, retired breeder, sham-operated and ovariectomized Sprague-Dawley rats were left untreated for 12 weeks to establish cancellous osteopenia in the ovariectomized group. The animals were then administered saline, low dose nicotine (6.0 mg/kg/day) or high dose nicotine (9.0 mg/kg/day) via osmotic minipumps for 12 weeks. Vertebrae and femora were collected at necropsy for determination of bone mass and strength. As expected, ovariectomy had a negative effect on most endpoints evaluated. Vertebral body bone mineral content (BMC) and density (BMD) and the structural (ultimate load and yield load) and material (ultimate stress, yield stress, and flexural modulus of elasticity) strength properties were lower in the OVX rats than in the sham-operated rats. Femoral diaphysis BMC, BMD, ultimate load, and flexural modulus were also lower in the OVX rats than in the sham-operated rats. The nicotine doses administered resulted in serum nicotine levels that averaged 1.5-4.5-fold greater than those observed in heavy smokers. Despite the high doses used, nicotine had no effect on vertebral BMC, BMD, or any of the structural and material strength properties in either the OVX or the Sham rats. In addition, nicotine had no effect on femoral diaphysis BMC, BMD, ultimate load, stiffness, ultimate stress, or flexural modulus. Femoral yield load and stress were lower in low dose nicotine-treated rats than in vehicle-treated rats. However, differences were not detected between the high dose nicotine- and vehicle-treated rats for either femoral yield load or stress. The results suggest that tobacco agents other than nicotine are responsible for the decreased bone density and increased fracture risk as observed in smokers.

Aging↗
PubMed2002

Effects of nicotine on bone and calciotropic hormones in aged ovariectomized rats.

The objective of this investigation was to assess the effects of chronic nicotine administration on bone status and serum calcium and calciotropic hormone levels in aged, estrogen-replete (intact, sham-operated) and estrogen-deplete (ovariectomized) female rats. Eight-month-old sham-operated (sham) and ovariectomized (ovx) retired breeder rats were maintained untreated for 3 months to allow for the development of osteopenia in the ovx group. The animals were then administered either saline, low dose nicotine (6.0 mg/kg/day), or high dose nicotine (9.0 mg/kg/day) via osmotic minipumps for 3 months. Blood was drawn at necropsy for determination of serum nicotine, cotinine, Ca, PTH, 25(OH)D, and 1,25(OH)(2)D. Right tibiae were collected and processed undecalcified for cancellous and cortical bone histomorphometry. Histomorphometric endpoints evaluated at the proximal tibial metaphysis included cancellous bone volume (BV/TV), osteoclast surface (Oc.S), osteoid surface (OS), mineralizing surface (MS), mineral apposition rate (MAR), and bone formation rate (BFR). Histomorphometric endpoints evaluated at the tibial diaphysis included cortical area (Ct.Ar), marrow area (Ma.Ar), and periosteal and endocortical MS, MAR, and BFR. Ovariectomy resulted in lower cancellous BV/TV and Ct.Ar and higher cancellous, endocortical, and periosteal MS and BFR. The presence of nicotine in serum confirmed successful delivery of the drug via osmotic minipumps. Administration of nicotine at the high dose resulted in lower serum 25(OH)D levels but differences in serum Ca or PTH were not detected with either nicotine treatment. Differences with nicotine treatment were also not detected for Oc.S at the proximal tibia. While treatment with nicotine at the high dose resulted in higher MS and BFR, in both sham and ovx rats, there were no differences due to nicotine treatment in cancellous BV/TV. Marrow area was greater in rats treated with nicotine than in rats treated with vehicle. However, differences with nicotine treatment were not detected in Ct.Ar in either intact or ovx rats. Overall, these findings indicate that steady state nicotine exposure does not alter bone mass in intact or ovx rats but may have detrimental effects on body storage of vitamin D.

Journal Article↗
PubMed2001

Effects of nicotine on bone mass, turnover, and strength in adult female rats.

This study investigated the effects of nicotine, the chemical responsible for tobacco addiction, on bone and on serum mineral and calcitropic hormone levels in adult, female rats to help resolve a current controversy regarding the impact of nicotine on bone health. Seven-month-old rats received either saline (n = 12), low-dose nicotine (4.5 mg/kg/day, n = 2), or high-dose nicotine (6.0 mg/kg/day, n = 12) administered subcutaneously via osmotic minipumps for 3 months. Blood, femora, tibiae, and lumbar vertebrae (3-5) were collected at necropsy for determination of serum mineral and hormonal concentrations, bone density (femora and vertebrae), bone turnover (tibiae), and bone strength (femora). The presence of nicotine in serum (111 +/- 7 and 137 +/- 10 ng/ml for the low- and high-dose nicotine groups, respectively) confirmed successful delivery of the drug via osmotic minipumps. Nicotine-induced treatment differences were not detected in serum calcium, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D. However, serum phosphorus and parathyroid hormone (PTH) were higher in rats treated with high-dose nicotine, and serum calcitonin was lower in rats treated with both high- and low-dose nicotine than in control rats. Nicotine treatment had no effect on tibial cancellous or cortical bone turnover or femoral bone mineral content (BMC) and density (BMD). Femoral ultimate load and vertebral BMC were lower in rats treated with high-dose nicotine than in control rats. We conclude that nicotine at serum concentrations 2.5-fold greater than the average in smokers has limited detrimental effects on bone in normal, healthy female rats.

Absorptiometry, Photon↗
PubMed2001

Growth suppression of established human osteosarcoma lung metastases in mice by aerosol gene therapy with PEI-p53 complexes.

Lung metastases are a frequent complication of osteosarcoma and a treatment that would reduce the severity of this complication would be of great benefit to patients. We have used a formulation consisting of polyethyleneimine (PEI) and a p53 gene administered in aerosol to treat established lung micrometastases as a model of human osteosarcoma in nude mice. The SAOS-LM6 cell line, a metastatic derivative of the p53 null SAOS-2 line, expresses high levels of p53 protein after in vitro transfection with PEI-p53 complexes as determined by ELISA, and transfection with both p53wt and the p53 variant, p53-CD(1-366) in vitro, results in a marked inhibition of SAOS-LM6 cell proliferation. Aerosol delivery of plasmid DNA containing either the p53 gene or a p53-CD(1-366) variant gene formulated with PEI to mice resulted in highly significant reductions in the numbers and size of tumors (P<.001), the total number of tumor foci in the lungs (P<.001) and the size of individual tumor nodules in treated animals compared to untreated, PEI only-treated and PEI-CAT-treated control animals. The different tissues examined did not reveal any signs of toxicity or inflammation after repeated exposure to PEI-DNA. The aerosol delivery of PEI-based formulations of p53 or synthetic p53 variant genes represents a promising new strategy for the treatment of established human osteosarcoma lung metastases. The noninvasive nature of aerosol delivery coupled with low toxicity also make this therapeutic approach potentially appropriate for combination therapy with either radio- or chemotherapy.

Administration, Inhalation↗
PubMed2000

Effects of nicotine on bone and calciotropic hormones in growing female rats.

Limited research in young adults and immature animals suggests a detrimental effect of tobacco on bone during growth. This study investigated the effects of nicotine, the major alkaloid component of tobacco, on calciotropic hormone concentrations and bone status in growing female rats. One-month-old animals received either saline (n = 10), nicotine at 3.0 mg/kg/day (n = 10), or nicotine at 4.5 mg/kg/day (n = 10) administered subcutaneously via osmotic minipumps for either 2 or 3 months. Sera, femora, tibiae, and lumbar vertebrae (3-5) were collected at necropsy. The concentrations of serum calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, calcitonin, and insulin-like growth factor-I were determined. Bone variables evaluated included mineral content and density (vertebrae and femora), cancellous and cortical histomorphometry (tibiae), and bone strength (vertebrae and femora). Statistically significant differences in serum mineral and hormone concentrations were not associated with nicotine dose or exposure time. No significant nicotine treatment effects were detected for bone mineral content and density, bone histomorphometry, or bone strength. We conclude that nicotine treatment for 2 or 3 months at serum concentrations in the upper range of those found in smokers has no detrimental effect on bone mass, volume, or strength in the growing rat.

Animals↗
PubMed1999

Activation of p53 tumor suppressor by hepatitis C virus core protein.

In addition to being a structural protein that packages the viral genomic RNA, hepatitis C virus (HCV) core protein possesses regulatory functions. In this report, we demonstrate that the HCV core protein could enhance the gene transactivation activity of the tumor suppressor p53, regardless of whether p53 was derived from an exogenous or an endogenous gene. The activation of p53 by the HCV core protein was supported by the observation that the HCV core protein could enhance the expression of p21(waf1/Cip1), a downstream effector gene of p53, in a p53-dependent manner. Further studies indicated that the HCV core protein could also suppress hepatocellular growth via p53. The HCV core protein and p53 could bind to each other in vitro, which was evidenced by the coimmunoprecipitation, the GST pull-down, and the Far-Western blot assays. The deletion-mapping analysis indicated that the carboxy-terminal sequence of p53 located between amino acids 366 and 380 was required for the core protein binding. These results raised the possibility that the HCV core protein might activate p53 through direct physical interaction. The persistent perturbation of p53 activity by the HCV core protein during chronic infection may have important consequences in HCV pathogenesis.

Carcinoma, Hepatocellular↗
PubMed1999

Discovery of a regulatory motif that controls the exposure of specific upstream cyclin-dependent kinase sites that determine both conformation and growth suppressing activity of pRb.

The conformation and activity of pRb, the product of the retinoblastoma susceptibility gene, is dependent on the phosphorylation status of one or more of its 16 potential cyclin-dependent kinase (cdk) sites. However, it is not clear whether the phosphorylation status of one or more of these sites contributes to the determination of the various conformations and activity of pRb. Moreover, whether and how the conformation of pRb may regulate the phosphorylation of the cdk sites is also unclear. In the process of analyzing the function and regulation of pRb, we uncovered the existence of an unusual structural motif, m89 (amino acids 880-900), the mutation of which confers upon pRb a hypophosphorylated conformation. Mutation of this structural domain activates, rather than inactivates, the growth suppressor function of pRb. In order to understand the effect of the mutation of m89 on the phosphorylation of cdk sites, we identified all the cdk sites (Thr-356, Ser-807/Ser-811, and Thr821) the phosphorylation of which drastically modify the conformation of pRb. Mutation of each of these four sites alone or in combinations results in the different conformations of pRb, the migration pattern of which, on SDS-polyacrylamide gel electrophoresis, resembles various in vivo hypophosphorylated forms. Each of these hypophosphorylated forms of pRb has enhanced growth suppressing activity relative to the wild type. Our data revealed that the m89 structural motif controls the exposure of the cdk sites Ser-807/Ser-811 in vitro and in vivo. Moreover, the m89 mutant has enhanced growth suppressing activity, similar to a mutant with alanine substitutions at Ser-807/Ser-811. Our recent finding, that the m89 region is part of a structural domain, p5, conserved antigenically and functionally between pRb and p53, suggests that the evolutionarily conserved p5 domain may play a role in the coordinated regulation of the activity of these two tumor suppressors, under certain growth conditions.

Amino Acid Sequence↗
PubMed1999

Long-term effects of nicotine on bone and calciotropic hormones in adult female rats.

This study determined the effects of nicotine on serum concentrations of several calciotropic hormones, and bone formation and resorption end-points in 7 month old, adult female rats. Animals were administered either saline (n= 9/group), low dose nicotine at 3.0 mg/kg/day (n=10/group) or high dose nicotine at 4.5 mg/kg/day (n=11/group) by subcutaneous osmotic minipumps. At the end of a three months treatment period, serum concentrations of calcium, phosphorus, parathyroid hormone, calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were determined. Femora, tibiae, and lumbar vertebrae (3-5) were collected and bone parameters evaluated included mineral density and content (femora and vertebrae), strength (femora and vertebrae) and histomorphometry (tibiae). Animals given nicotine had significantly lower levels of 25-hydroxyvitamin D than controls [20.8+/-1.4 ng/ml for the low dose group and 20.7+/-1.0 ng/ ml for the high dose group versus 27.6+/-1.3 ng/ml for the control group (mean+/-S.E.M.), P<0.01]. The high dose nicotine group had smaller vertebral areas (5.4+/-0.2 mm2 versus 6.2+/-0.2 mm2, P<0.05) and a lower bone mineral content than the controls (0.024+/-0.001 g versus 0.030+/-0.001 g, P<0.05). Tibial endocortical mineral apposition rate was also significantly lower in the high dose nicotine group than in the control group (1.06+/-0.13 microm/day versus 1.42+/-0.08 microm/day. P<0.05). No significant treatment differences were detected in bone density, cancellous bone histomorphometry, or bone strength. Results from the present study suggest that nicotine administration may adversely affect bone formation and decrease body storage of vitamin D.

Animals↗
PubMed1999

Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins.

Human cyclin A1, a newly discovered cyclin, is expressed in testis and is thought to function in the meiotic cell cycle. Here, we show that the expression of human cyclin A1 and cyclin A1-associated kinase activities was regulated during the mitotic cell cycle. In the osteosarcoma cell line MG63, cyclin A1 mRNA and protein were present at very low levels in cells at the G0 phase. They increased during the progression of the cell cycle and reached the highest levels in the S and G2/M phases. Furthermore, the cyclin A1-associated histone H1 kinase activity peaked at the G2/M phase. We report that cyclin A1 could bind to important cell cycle regulators: the Rb family of proteins, the transcription factor E2F-1, and the p21 family of proteins. The in vitro interaction of cyclin A1 with E2F-1 was greatly enhanced when cyclin A1 was complexed with CDK2. Associations of cyclin A1 with Rb and E2F-1 were observed in vivo in several cell lines. When cyclin A1 was coexpressed with CDK2 in sf9 insect cells, the CDK2-cyclin A1 complex had kinase activities for histone H1, E2F-1, and the Rb family of proteins. Our results suggest that the Rb family of proteins and E2F-1 may be important targets for phosphorylation by the cyclin A1-associated kinase. Cyclin A1 may function in the mitotic cell cycle in certain cells.

Animals↗
PubMed1998

Modulation of nigrostriatal dopaminergic transmission by antisense oligodeoxynucleotide against brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) promotes the differentiation and growth of developing dopamine (DA) neurons and supports the survival of mature DA cells in culture. However, the neurotrophic role of endogenous BDNF in the adult DA system in vivo has not been well established. To investigate the hypothesis that blockade of endogenous BDNF expression results in DA dysregulation, we used an 18-mer antisense oligodeoxynucleotide (ODN) targeted to the first ATG codon of the BDNF transcript. The biological activity of the antisense ODN was initially tested in vitro. In cultured dopaminergic MES 23.5 cells, antisense BDNF (20 microM) effectively reduced BDNF protein expression and cell survival. Furthermore, in primary embryonic mesencephalic cultures, antisense BDNF reduced the number of tyrosine hydroxylase positive neurons and inhibited [3H]DA uptake in a time- and dose-dependent manner. The specificity of the antisense molecule was confirmed by comparing its effects with those of a control ODN having the same base composition but in scrambled sequence. In rats, two days following an intranigral or intrastriatal injection of antisense BDNF (0.5 microg), we observed a two-fold and five-fold increase in nigral DA levels, respectively, but no change in striatal DA content. Seven days after an intrastriatal antisense BDNF injection, DA levels were elevated in the striatum apparently due to decreased DA turnover. These observations suggest that inhibition of endogenous BDNF expression tends to augment rather than inhibit nigrostriatal DA transmission. Thus, the biological effects of endogenous BDNF on the nigrostriatal DA system in the adult organism merits further investigation.

Animals↗
PubMed1998

Short-term effects of nicotine on bone and calciotropic hormones in adult female rats.

This study assessed the effects of two months nicotine treatment on bone formation and resorption end-points in adult, female rats. In addition, the concentrations of calciotropic hormones which included parathyroid hormone, calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in rats (7 months old) were determined. All animals received either saline (n = 7/group), nicotine (3.0 mg/kg/day) (n = 7/group) or nicotine (4.5 mg/kg/day) (n = 7/group) via subcutaneous implantation of osmotic minipumps containing either saline or nicotine for a period of two months. Serum, right tibia, left femur and lumbar vertebra (3-5) were collected for determination of hormonal concentrations as well as various parameters, including histomorphometry, bone mineral density, bone mineral content and vertebral strength. Although nicotine-treated rats showed a lower level of 25-hydroxyvitamin D [54.4 +/- 3.1 ng/ml for the 3.0 mg/kg/day and 55.8 +/- 2.8 for the 4.5 mg/kg/day group] (mean +/- S.E.M.) as compared to controls (74.8 +/- 2.8 ng/ml) (P < 0.01, Newman-Keuls test), no significant difference could be detected for the levels of the remaining hormones. Similarly, no statistical differences were detected on histomorphometric end-points, bone mineral density, bone mineral content and vertebral strength of rats. We conclude that, in spite of lowering serum 25-hydroxyvitamin D by about 30%, nicotine administration of two months duration does not alter bone mass, strength or formation and resorption end-points.

Animals↗
PubMed1997

Engineered mutants of pRB with improved growth suppression potential.

We have constructed a panel of substitution mutants which affect one or more of the putative cdk target sites of the RB protein. We have examined the activity of these mutants relative to wild-type RB by both a transcriptional repression assay and by measuring growth suppression in vitro. We find that some phosphorylation site mutants of pRB can repress E2 transcription more strongly than wild-type RB. These mutants are partially resistant to phosphorylation by cdks and can arrest tumor cells in G1 in vitro. Our results indicate a functional correlation between the ability to repress E2F-dependent transcription and the ability to suppress tumor cell growth in vitro. In addition, we describe two classes of RB mutants: N-terminal truncated p56RB and a novel mutant of RB containing multiple substitutions near its nuclear localization signal. Both classes of RB mutants have greater activity than the wild-type protein. Because RB is a key regulator of cell cycle progression, expression of a more potent, phosphorylation resistant RB may have utility in both RB(-/-) and RB(+/+) tumors as well as in hyperproliferative disorders.

Amino Acid Substitution↗
PubMed1997

Antagonistic effects of isofloxythepin on dopamine D1 and D2 receptors and behaviors in rats.

1. In vitro, isofloxythepin competed for the binding of [3H]SCH 23390 to striatal D1 receptors and for the binding of [3H]spiperone to striatal D2 receptors with IC50 values of 6.1 (+/- 1.2) x 10(-10)M and 8.4 (+/- 2.6) x 10(-10)M, respectively. Isofloxythepin further inhibited the D1 receptor-mediated, dopamine-stimulated adenylate cyclase in the striatal tissue. 2. Fifteen hours after rats were injected with a single dose of isofloxythepin (1 mg/kg, SC), the ex vivo binding curve of [3H]spiperone to striatal D2 receptors was markedly inhibited, whereas the binding curve of [3H]SCH 23390 to striatal D1 receptors was unaffected. 3. Fifteen hours after isofloxythepin pretreatment, D1 agonist SKF 38393 (15 mg/kg, IP)-stimulated grooming behavior was not affected, whereas the D2 agonist quinpirole (3 mg/kg, IP)-stimulated stereotyped behavior was completely abolished. 4. On the basis of the findings from in vivo studies, we conclude that, although isofloxythepin is found to have high affinity for both D1 and D2 receptors in vitro, it lacks D1 antagonistic potency in vivo.

Adenylyl Cyclases↗
PubMed1997

Brain mercury in neurodegenerative disorders.

BACKGROUND: Trace element neurotoxicity has long been invoked as an etiologic factor for Alzheimer's disease. This study was conducted to determine the concentrations of mercury in seven different brain regions from deceased patients histologically confirmed with Alzheimer's disease or multiple sclerosis as compared to control subjects without known central nervous system and renal disorders. Brain mercury concentrations in all deceased subjects can arise from amalgam restorations, diet, and the working environment. METHODS: Autopsy frozen specimens (control, Alzheimer's disease and multiple sclerosis) from seven brain regions, which included frontal cortex, temporal cortex, occipital cortex, putamen, hippocampus, corona radiata and corpus callosum were assayed for the concentrations of selenium using instrumental neutron activation analysis and mercury using radiochemical neutron activation analysis. RESULTS: We found that the concentrations of mercury and the mercury/selenium molar ratios were significantly lower in the hippocampi of multiple sclerosis patients as compared to aged-matched controls. However, no statistically significant differences were detected for the concentrations of mercury and the mercury/ selenium molar ratios for the remaining six brain regions among these groups. CONCLUSIONS: Since brain mercury concentrations from deceased subjects with either Alzheimer's disease or multiple sclerosis are not significantly higher than controls, the present study provides no scientific support that mercury plays a significant role in the pathogenesis of these neurologic disorders.

Aged↗
PubMed1996

Effects of nicotine withdrawal on central dopaminergic systems.

The behavioral and neurochemical manifestations in rats 24 h following the cessation of 14-day nicotine administration were investigated. Animals were implanted subcutaneously with osmotic minipumps which continuously released either saline or nicotine (1.5 mg/kg/day or 3.0 mg/kg/day) for 14 days. After the animals were withdrawn from nicotine for 24 h, we observed a significant decrease of locomotor activities and a reduction of dopamine contents in the striatum and nucleus accumbens. Nicotine withdrawal did not affect the body weight, food, or water consumption, and no deficit in the acquisition of a conditioned avoidance task was found in these animals. In addition, nicotine withdrawal did not alter the density or the binding affinity (Kd) of ligands to D1 and D2 receptors in the striatum. Although nicotine withdrawal did not alter the density or binding affinity of ligands to D1 receptors in the nucleus accumbens, the maximum number of D2 receptor sites were reduced by nicotine treatment. These results offer possible neurochemical mechanisms for changes of locomotor activity which occurred in rats during nicotine abstinence.

Animals↗
PubMed1995

Inhibition of apoptosis by the retinoblastoma gene product.

Tissue homeostasis and the prevention of neoplasia require regulatory co-ordination between cellular proliferation and apoptosis. Several cellular proteins, including c-myc and E2F, as well as viral proteins such as E1A, have dual functions as positive regulators of apoptosis and proliferation. The product of the retinoblastoma tumor suppressor gene, pRb, binds these proteins and is known to function in growth suppression. To examine whether pRb may function as a negative regulator of both proliferation and apoptosis, we analyzed apoptosis induced in transfected derivatives of the human osteosarcoma cell line SAOS-2. Ionizing radiation induced apoptosis in a time- and dose-dependent manner in SAOS-2 cells, which lack pRb expression. In both a transient and stable transfection assay, SAOS-2 derivatives expressing wild-type (wt) pRb exhibited increased viability and decreased apoptosis following treatment at a variety of radiation doses. Expression in SAOS-2 of a mutant pRb that fails to complex with several known binding partners of pRb, including E1A and E2F, did not protect SAOS-2 cells from apoptosis. Radiation exposure induced a G2 arrest in SAOS-2 and in derivatives expressing pRb. Inhibition of DNA synthesis and cell cycle progression by aphidicolin treatment failed to protect SAOS-2 cells or pRb-expressing isolates from undergoing apoptosis. Our data document a novel function for pRb in suppressing apoptosis and suggest that several proteins shown to induce apoptosis, including E1A, E2F and c-myc, may do so by interfering with the protective function of pRb.

Aphidicolin↗