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PubMed1995

Differential effects of prostaglandin E1 and prostaglandin E2 on growth and differentiation of murine myeloid leukemic cell line, M1.

Effects of prostaglandins (PGs) of the E series on growth and differentiation of murine myeloid leukemic cell line M1 were studied. PGE1, but not PGE2, inhibited the growth of M1 cells. PGE2 neither inhibited nor augmented the antiproliferative effect of PGE1. PGE1 augmented the differentiation of M1 cells into macrophage-like cells induced by interleukin 6. PGE2, however, did not exhibit any effect on the differentiation. PGE1 caused a marked increased in intracellular cAMP level in M1 cells, whereas PGE2 had no effect. These results indicate that M1 cells are able to respond only to PGE1. Radiolabeled PGE1 binding experiments, however, revealed that there was no specific binding in M1 cells, suggesting that the cells express low numbers of receptors or very low affinity receptors specific for PGE1. Stable agonists of PGI2, iloprost, cicaprost or carbacyclin, also potently inhibited the growth of M1 cells. These findings suggest that PGE1 as well as PGI2 may play a role in the differentiation of monocyte-macrophage lineage cells.

Alprostadil↗
PubMed1994

Macrophage colony-stimulating factor induces the growth and differentiation of normal pregnancy human cytotrophoblast cells and hydatidiform moles but does not induce the growth and differentiation of choriocarcinoma cells.

In the present study, we examined whether or not macrophage colony-stimulating factor (M-CSF; CSF-1) is involved in the growth and differentiation of human chorionic, hydatidiform mole and choriocarcinoma cells. M-CSF promotes the growth of early gestation chorionic cells, hydatidiform mole cells, and a human term placenta cell line (tPA30-1). However, the growth of choriocarcinoma cells, BeWo, Jar, Jeg-3, and NUC-1, was not influenced at all by M-CSF. M-CSF promoted the secretion of human chorionic gonadotropin (hCG) and human placental lactogen (hPL), which are secreted from differentiated trophoblast, from early gestation chorionic cells and from hydatidiform mole cells. However, the secretion of hCG and hPL from choriocarcinoma cells was not affected by M-CSF. When M-CSF localization was examined by immunohistochemical staining, M-CSF was detected in chorionic and hydatidiform mole cells, but was absent in choriocarcinoma cells. These results suggest that the growth and differentiation of normal chorionic and hydatidiform mole cells are M-CSF-dependent, while the growth and differentiation of choriocarcinoma cells are not.

Base Sequence↗
PubMed1986

Butyrate-induced cell differentiation of cell-cycle mutants and 'wild-type' mastocytoma cells: histamine, 5-hydroxytryptamine and metachromatic granules as independently regulated differentiation markers.

In cultures of heat-sensitive (hs; arrested at 39.5 degrees C, multiplying at 33 degrees C) and cold-sensitive (cs; arrested at 33 degrees C, multiplying at 39.5 degrees C) cell-cycle mutants that had been isolated from the same subclone (K21) of the murine P-815-X2 mastocytoma line, the degree of cell differentiation was assessed by determining the cellular histamine and 5-hydroxytryptamine (5-HT) content as well as the number of metachromatic granules per cell. The findings were compared with those obtained for 'wild-type' K21 and P-815-X2 cells. The addition of butyrate to 'wild-type' cells or to mutant cells maintained at the respective permissive temperature resulted in a relative increase in the level of all three differentiation markers. In cs mutant cells, essentially the same pronounced increase in granule numbers was observed during butyrate treatment at 39.5 degrees C and during incubation at 33 degrees C without butyrate, thereby suggesting that butyrate induces morphological cell differentiation in cs mutants via the same mechanisms as exposure to the nonpermissive temperature. In contrast, the histamine and 5-HT levels reached in hs and cs mutant cells in the presence of butyrate were higher than those observed during incubation at the nonpermissive temperature. Large quantitative differences were detected with respect to the potential of individual cell lines to express the three differentiation parameters. High levels of histamine were characteristic of 'wild-type' P-815-X2 cells treated at 33 degrees C with butyrate, while low amine levels and small numbers of granules were observed in K21 cells (i.e., the parent line of hs and cs mutants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Differential expression and localization of brain-type and mitochondrial creatine kinase isoenzymes during development of the chicken retina: Mi-CK as a marker for differentiation of photoreceptor cells.

The expression and the cellular- as well as subcellular-distribution of brain-type B-CK and mitochondrial Mi-CK during development of the chicken retina was studied by immunoblotting, immunofluorescence and immunogold methods. B-CK expression and accumulation in retina was high from early stages of embryonic development on, decreased slightly around hatching and remained high again during adulthood. At early stages of development (days 2-5), B-CK was more or less evenly distributed over the entire retina with the exception of ganglion cells, which were stained more strongly for B-CK than other retinal precursor cells. Then, at around day 10, the beginning of stratified immunostaining by anti-B-CK antibody was noted concomitant with progressing differentiation. Finally, a dramatic increase in staining of the differentiating photoreceptor cells was seen before hatching (day 18) with weaker staining of other cell types. At hatching, as in the adult state, most of the B-CK was localized within rods and cones. Thus, during retinal development marked changes in the immunostaining pattern for B-CK were evident. By contrast, Mi-CK expression was low during development in ovo and rose just before hatching with a predominant accumulation of this isoenzyme within the ellipsoid portion of the inner photoreceptor cell segments. Mi-CK accumulation in the retina coincided with functional maturation of photoreceptors and therefore represents a good marker for terminal differentiation of these cells. B-CK, present from early stages of retina development, seems to be relevant for the energetics of retinal cell proliferation, migration and differentiation, whereas the simultaneous expression of both B- and Mi-CK around the time of hatching indicates a coordinated function of the two CK isoforms as constituents of a PCr-circuit involved in the energetics of vision, which, in autophagous birds, has to be operational at this point in time.

Animals↗
PubMed1994

The effect of denervation on myosin isoform synthesis in rabbit slow-type and fast-type muscles during terminal differentiation. Denervation induces differentiation into slow-type muscles.

The soleus and gastrocnemius medialis of eight-day-old rabbits were denervated and the effects were examined after fifty-two days by biochemical, cytochemical and mechanical methods. The contralateral soleus exhibited the properties of slow-type muscle, namely a predominance of slow-type myosin isoforms and slow-type oxidative fibers, slow twitch and low maximal velocity for shortening. The contralateral gastrocnemius exhibited the properties of fast-type muscle, namely a predominance of fast-type myosin isoforms and fast-type non-oxidative fibers, fast twitch and high maximal velocity of shortening. Denervation of muscles caused the differentiation of the two muscles towards slow-type muscles. Both denervated soleus and gastrocnemius muscles exhibited a predominance of slow-type myosins (either the normal type, made up of slow heavy and light chains, or the hybrid type, made up of slow heavy and regulatory light chains and fast essential light chains), a predominance of slow-type fibers, and slow mechanical properties. Thus, innervation in rabbit appears to be a determining factor for differentiation into fast-type muscle, but it is not necessary for differentiation into slow-type muscle. This conclusion contradicts the findings of previous studies in rat and thus raises new questions concerning the role of nerves in controlling the expression of myosin isoforms and the differentiation of muscle fibers.

Animals↗
PubMed1988

Differentiation in acute myeloid leukemia and myelodysplastic disorders. Is differentiation-induction therapy possible?

In this review we have discussed the data which indicates that differentiation can indeed occur to a limited degree in the neoplastic cells in acute leukemia and myelodysplastic syndromes. Attempts to increase the degree of differentiation as an approach to the treatment of these disorders have utilised a variety of chemical agents which have been reported to exert such an effect in vitro. Analysis of the results, however, indicates that beneficial effects of these agents in patients is due to cytotoxic action which selectively reduces the neoplastic cell population. Leukemic cells can also undergo incomplete differentiation in vitro when exposed to appropriate growth factors, which raises the question of whether leukemia and myelodysplasia can be treated by the induction of differentiation in the malignant cells following the administration of these agents. This question, and questions about the nature of complete remission, will be answered in the coming years by clinical trials of growth factors, and further studies of the DNA in mature cells to analyse whether these cells are derived from leukemic progenitors.

Cell Differentiation↗
PubMed1987

Differential expression of alkaline phosphatase and ATPase activities in human colon carcinoma cell line HT-29.18 during differentiation.

The expression and cytochemical localization of alkaline phosphatase and Na+-pump sites were investigated in the human adenocarcinoma cell line HT-29.18 during differentiation. In the undifferentiated state, HT-29.18 cells expressed ATPase activity on plasma membrane whereas they displayed no alkaline phosphatase activity. In differentiated HT-29.18 cells, strong alkaline phosphatase activity was present on the apical membrane, whereas ATPase activity was restricted to the basolateral membrane. Intra- and intercellular lumina (cysts) observed in undifferentiated cells were devoid of both enzyme activities. In differentiated cells, cysts bearing well developed microvilli were strongly positive for alkaline phosphatase activity, while this activity seemed to be lacking in cysts without microvilli. ATPase activity was not found in either type of structure. Finally, HT-29.18 differentiated cells expressed, at pH 9.0, a p-nitrophenylphosphatase activity six-fold greater than that of undifferentiated cells.

Adenocarcinoma↗
PubMed1988

Vitamin D and epidermal differentiation: evidence for a role of endogenously produced vitamin D metabolites in keratinocyte differentiation.

Vitamin D3 is produced in the skin. It is metabolized primarily in the liver to the major circulating form 25-hydroxy vitamin D3, [25(OH)D3] which is metabolized in the kidney to produce the biologically active form of the hormone, 1,25-dihydroxy vitamin D3, [1,25(OH)2D3]. The skin not only participates in the production of vitamin D3 but also contains receptors for 1,25(OH)2D3 suggesting a role of this hormone in the growth and differentiation of this tissue. 1,25(OH)2D3 appears to play a role in epidermopoiesis and melanin pigmentation. Recently, using cultures of neonatal human foreskin keratinocytes, we have demonstrated that these cells produce abundant quantities of 1,25(OH)2D3 from 25(OH)D3. The production of 1,25(OH)2D3 varies with the degree of differentiation of keratinocytes and is regulated by exogenous 1,25(OH)2D3. 1,25(OH)2D3 induces differentiation possibly because of its ability to increase intracellular free calcium levels. A tentative model is provided to demonstrate potential mechanisms by which 1,25(OH)2D3-induced changes in intracellular calcium could regulate epidermal differentiation.

Animals↗
PubMed1983

Interferon-induced differentiation of U937 cells. Comparison with other agents that promote differentiation of human myeloid or monocytelike cell lines.

Effects of human fibroblast (beta) or leukocyte (alpha) interferon (IFN) on differentiations of a human histiocytic lymphoma-derived cell line (U937) or promyelocytic leukemia-derived cell line (HL-60) were studied. When cultured with beta-IFN (400-1,000 U/ml), U937 cells showed gross morphologic and microscopic changes consisting of clumping, increased cytoplasmic-to-nuclear ratio, enhanced prominence of cytoplasmic granules, and membrane ruffling. After culture with beta-IFN, the number of U937 cells reactive with B43.4.1 monoclonal antibody, which is specific for human monocytes, natural killer cells, and neutrophils, increased from less than 10% of U937 cells to 47% beta-IFN treatment also enhanced antibody-dependent cellular cytotoxicity against chicken erythrocytes by U937 cells. The same morphologic, phenotypic, and functional changes were also observed when U937 were treated with recombinant or natural alpha-IFN. The effects of alpha-IFN were totally abolished by anti-alpha-IFN serum. In contrast, HL-60, which differentiates toward cells of the monocyte lineage in response to phorbol 12-myristate 13-acetate (based on the above criteria), and toward granulocytes in response to dimethyl sulfoxide, did not differentiate when cultured with alpha- or beta-IFN. No consistent relationship between induction of differentiation and changes in phospholipid methylation were observed.

Antigens↗
PubMed2005

Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells.

The zinc finger transcription factor GATA-1 is essential for both primitive (embryonic) and definitive (adult) erythropoiesis. To define the roles of GATA-1 in the production and differentiation of primitive and definitive erythrocytes, we established GATA-1-null embryonic stem cell lines in which GATA-1 was able to be conditionally expressed by using the tetracycline conditional gene expression system. The cells were subjected to hematopoietic differentiation by coculturing on OP9 stroma cells. We expressed GATA-1 in the course of primitive and definitive erythropoiesis and analyzed the ability of GATA-1 to rescue the defective erythropoiesis caused by the GATA-1 null mutation. Our results show that GATA-1 functions in the proliferation and maturation of erythrocytes in a distinctive manner. The early-stage expression of GATA-1 during both primitive and definitive erythropoiesis was sufficient to promote the proliferation of red blood cells. In contrast, the late-stage expression of GATA-1 was indispensable to the terminal differentiation of primitive and definitive erythrocytes. Thus, GATA-1 affects the proliferation and differentiation of erythrocytes by different mechanisms.

Anti-Bacterial Agents↗
PubMed2002

Differential expression and phosphorylation of distinct STAT3 proteins during granulocytic differentiation.

External stimuli act in concert with intracellular signals to regulate a cell's genetic program, activating genes important in granulocytic lineage commitment, proliferation, and maturation. Signal transducer and activator of transcription 3 (STAT3), a transcription factor, has been implicated in mediating granulocytic differentiation. We have examined the role of STAT3 as a physiologic mediator of granulocytic kinetics. Distinct isoforms--the long form STAT3 alpha, the truncated forms STAT3 beta and STAT3 gamma, and a putative novel form STAT3 delta--were expressed and activated in a maturation stage-specific manner. With the progression of differentiation, the ratio of isoforms shifted from predominantly STAT3 alpha to STAT3 beta. The kinetics of STAT3 gamma, generated through proteolytic cleavage of STAT3 alpha, coincided with but were inverse to those of STAT3 alpha. STAT3 delta was expressed at low levels and decreased with differentiation but was preferentially phosphorylated during an intermediate stage of maturation. Under different culture conditions (pH, O(2) tension [pO(2)], IL-3), we found that the expression and phosphorylation status of the different STAT3 isoforms displayed unique kinetic patterns that correlated with the effects on granulocyte differentiation. The evidence suggests that signals triggered by pH, pO(2), and IL-3 each converge on STAT3 through independent mechanisms, exploiting the flexibility granted by the diversity in expression and phosphorylation of the different STAT3 isoforms, to regulate distinct granulocytic cell responses. The selective expression of STAT3 isoforms and their activation is a major determinant of granulocytic cell development and provides a molecular basis for evaluating the effects of various environmental factors on the STAT3-mediated signaling pathway.

Antigens, CD34↗
PubMed2001

Differentiation of monocytes into multinucleated giant bone-resorbing cells: two-step differentiation induced by nurse-like cells and cytokines.

Bone resorption in the joints is the characteristic finding in patients with rheumatoid arthritis (RA). Osteoclast-like cells are present in the synovial tissues and invade the bone of patients with RA. The characteristics of these cells are not completely known. In the work reported here, we generated these cells from peripheral-blood monocytes from healthy individuals. The monocytes were co-cultured with nurse-like cells from synovial tissues of patients with RA (RA-NLCs). Within 5 weeks of culture, the monocytes were activated and differentiated into mononuclear cells positive for CD14 and tartrate-resistant acid phosphatase (TRAP). These mononuclear cells then differentiated into multinucleated giant bone-resorbing cells after stimulation with IL-3, IL-5, IL-7, and/or granulocyte-macrophage-colony-stimulating factor. TRAP-positive cells with similar characteristics were found in synovial fluid from patients with RA. These results indicate that multinucleated giant bone-resorbing cells are generated from monocytes in two steps: first, RA-NLCs induce monocytes to differentiate into TRAP-positive mononuclear cells, which are then induced by cytokines to differentiate into multinucleated giant bone-resorbing cells.

Acid Phosphatase↗
PubMed1988

Differential effects of 1 alpha,25-dihydroxycholecalciferol and 24R,25-dihydroxycholecalciferol on the proliferation and the differentiated phenotype of rabbit costal chondrocytes in culture.

1 alpha,25-Dihydroxycholecalciferol [1,25-(OH)2D3] stimulated the proliferation and DNA synthesis of rabbit costal growth cartilage cells in the logarithmic growth phase in culture. The stimulatory effects of 1,25-(OH)2D3 were observable at a concentration of 10(-10) M and maximal at a concentration of 10(-8) M. On the other hand, 1,25-(OH)2D3 inhibited their expression of the cartilage phenotype, as judged morphologically, histochemically, and biochemically by a decrease in glycosaminoglycan (GAG) synthesis. The inhibition of GAG synthesis was also dose dependent and observable at a concentration of 10(-10) M. 1,25-(OH)2D3 also stimulated the proliferation of resting cartilage cells and inhibited their GAG synthesis, but its effects on these cells were less than those on growth cartilage cells, suggesting that 1,25-(OH)2D3 acts more specifically on growth cartilage cells than on resting cartilage cells. 1,25-(OH)2D3 had no effect on either DNA synthesis or GAG synthesis of growth cartilage cells in confluent cultures. 24R,25-Dihydroxycholecalciferol [24,25-(OH)2D3] had no effect on proliferation, DNA synthesis, or GAG synthesis of growth cartilage cells in the logarithmic growth phase. However, 24,25-(OH)2D3 had no effect on DNA synthesis of these cells in confluent cultures, but stimulated their expression of the cartilage phenotype. The stimulatory effect was dose dependent and maximal at 10(-7) M. Since chondrocytes express their differentiated phenotype as they become confluent in culture, these results suggest that 1,25-(OH)2D3 stimulates the growth of rapidly proliferating chondrocytes with a poorly differentiated phenotype and suppresses their expression of the cartilage phenotype, while 24,25-(OH)2D3 stimulates expression of the differentiated phenotype of highly differentiated chondrocytes.

24,25-Dihydroxyvitamin D 3↗
PubMed1989

The role of prostaglandins in masculine differentiation: modulation of prostaglandin levels in the differentiating genital tract of the fetal mouse.

The present study was designed to test the hypothesis that the stimulation of arachidonic acid prostaglandins (PG) mediates the masculinizing effects of testosterone in the fetal mouse. We examined a number of situations in which masculine organization was either induced or inhibited by external agents and determined whether PG levels in the fetal genital tracts were altered in a manner coincident with those situations. We show here that both PGE2 and 6-keto-PGF1 alpha levels in the male fetal genital tracts increased with the advancement of masculine differentiation. PG levels in males (1.2 +/- 0.3 pg PGE2 and 0.1 +/- 0.03 pg 6-keto-PGF1 alpha on day 14 of gestation) increased to 2.1 +/- 0.3 pg PGE2 and 1.2 +/- 0.3 PG 6-keto-PGF1 alpha on day 18 of gestation. The PG levels in the male genital tract were significantly higher than the PG levels in the female genital tract throughout the period of sexual differentiation. Before this period, however, such as on day 14 of gestation (when male and female fetuses have identical genital tracts) we found no difference in their PG levels. Moreover, administration of testosterone (40 mg/kg) during the critical period of masculine differentiation (days 13-17 of gestation) significantly increased PG levels (approximately 2-fold) of female fetuses. Furthermore, we found that cyproterone acetate (20 mg/kg), an inhibitor of masculine differentiation, on days 13-17 of gestation deceased PG levels in male fetuses. In addition, administration of PG synthesis inhibitors, namely indomethacin (1 mg/kg) and aspirin (100 mg/kg), inhibited both resting and androgen-inducible PG levels in male and female fetuses. Considering these results together, it may be concluded that PGs have a critical role in the masculinizing action of fetal testosterone.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Differential regulation of steroidogenic enzymes during differentiation optimizes testosterone production by adult rat Leydig cells.

The postnatal differentiation of rat Leydig cells may be subdivided into three stages based on morphology and steroid production. The purpose of this study was to clarify the developmental mechanisms underlying increased testosterone production by measuring steady state levels of the mRNAs for three steroidogenic enzymes in isolated Leydig cells at each stage of differentiation. These include Leydig cell progenitors on day 21, immature Leydig cells on day 35, and adult Leydig cells on day 90. The steroidogenic enzymes were 1) cholesterol side-chain cleavage enzyme (CSCC), 2) 17 alpha-hydroxylase (P450-17 alpha), and 3) 3 alpha-hydroxysteroid dehydrogenase (3 alpha HSD). We report that levels of CSCC and P450-17 alpha mRNAs increase, whereas 3 alpha HSD mRNA levels decline during the course of Leydig cell differentiation. The levels of 3 alpha HSD mRNA were high in progenitor Leydig cells that appeared to contain little smooth endoplasmic reticulum and decreased in cells as smooth endoplasmic reticulum developed and other enzyme mRNAs increased. These observations suggest that the factors that regulate 3 alpha HSD mRNA levels are startlingly different from those that regulate the mRNA levels of CSCC and P450-17 alpha. We conclude that the progressive increase in the capacity of differentiating Leydig cells to produce testosterone can be explained in part by an increase in the activity of enzymes that synthesize testosterone (CSCC and P450-17 alpha) and a decrease in the activity of an enzyme that metabolizes testosterone and its precursors (3 alpha HSD).

3-Hydroxysteroid Dehydrogenases↗
PubMed1999

Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes.

Both bone mass and serum leptin levels are increased in obesity. Because osteoblasts and adipocytes arise from a common precursor in bone marrow, we assessed the effects of human recombinant leptin on a conditionally immortalized human marrow stromal cell line, hMS2-12, with the potential to differentiate to either the osteoblast or adipocyte phenotypes. By RT-PCR and Western immunoblot analysis, the hMS2-12 cells expressed messenger RNA (mRNA) and protein for the leptin receptor. Leptin did not affect hMS2-12 cell proliferation, but resulted in dose- and time-dependent increases in mRNA and protein levels of alkaline phosphatase, type I collagen, and osteocalcin, and in a 59% increase in mineralized matrix. Leptin increased mRNA levels of lipoprotein lipase at 3 days, but decreased mRNA levels of adipsin and leptin at 9 days and decreased lipid droplet formation by 50%. Leptin did not affect the expression of Cbfa1 or peroxisome proliferator-activated receptor-gamma2, transcription factors involved in commitment to the osteoblast and adipocyte pathways, respectively. Thus, leptin acts on human marrow stromal cells to enhance osteoblast differentiation and to inhibit adipocyte differentiation. Our data support the hypothesis that leptin is a previously unrecognized, physiological regulator of these two differentiation pathways, acting primarily on maturation of stromal cells into both lineages.

Adipocytes↗
PubMed2002

Estrogen promotes early osteoblast differentiation and inhibits adipocyte differentiation in mouse bone marrow stromal cell lines that express estrogen receptor (ER) alpha or beta.

Although cells of the osteoblast lineage express functional ERs, direct effects of estrogen on bone formation remain obscure. In the present study, we have investigated estrogen effects on osteoblastic and adipocytic differentiation from a mouse bone marrow stromal cell line, ST-2, which had been manipulated to overexpress either human ER alpha (ST2ER alpha) or ER beta (ST2ER beta). Treatment with bone morphogenetic protein-2 increased alkaline phosphatase activity as well as the number of Oil Red O-positive adipocytes, indicating that bone morphogenetic protein-2 stimulated both osteoblastic and adipocytic differentiation from these bipotential cells. In both ST2ER alpha and ST2ER beta cells, cotreatment with E2 caused enhancement of alkaline phosphatase activity and suppression of lipid accumulation. These effects were completely reversed by an ER antagonist, ICI182780. Therefore, the estrogen regulation occurred in an ER-specific manner but without ER subtype specificity. Moreover, dose response curves of the opposing effects of estrogen on osteoblastogenesis and adipogenesis formed an apparent mirror image, consistent with a reciprocal regulation of differentiation into the two cell lineages. These results demonstrate that estrogen directly modulates differentiation of bipotential stromal cells into the osteoblast and adipocyte lineages, causing a lineage shift toward the osteoblast. Such effects would lead to direct stimulation of bone formation and thereby contribute to the protective effects of estrogen on bone.

Adipocytes↗
PubMed2001

Interaction of IGF-binding protein-related protein 1 with a novel protein, neuroendocrine differentiation factor, results in neuroendocrine differentiation of prostate cancer cells.

Neuroendocrine cells have been implicated in many cancers, including small cell lung, cervical, breast, and prostate carcinomas. The increase in neuroendocrine cell number in prostate cancer has been reported to correlate with poor prognosis, progressive tumors, and androgen insensitivity. The mechanisms involved in this differentiation remain unknown. IGF-binding protein-related protein 1 is a member of the IGF-binding protein superfamily and has recently been shown to exhibit differentiation and tumor suppression activity in prostate cancer cell lines stably overexpressing IGF-binding protein-related protein 1. From a yeast two-hybrid screen, a novel IGF-binding protein-related protein 1-interacting protein was identified. Immunocytochemical techniques indicate that this protein, 25.1, and intracellular IGF-binding protein-related protein 1 colocalize in the nucleus. When 25.1 is transiently expressed in a stable prostate cancer cell line overexpressing IGF-binding protein-related protein 1, cells assume a neuritic-like morphology with long dendritic-like processes and express the neuroendocrine markers chromogranin A and neuron-specific enolase. We propose that 25.1 (neuroendocrine differentiation factor) together with IGF-binding protein-related protein 1 can induce neuroendocrine cell differentiation in prostate cancer cells.

Amino Acid Sequence↗