Expression Of aFGF Research Articles

Morphological, Immunohistochemical, and Ultrastructural Studies of the Donkey's Eye with Special Reference to the AFGF and ACE Expression.

The donkey is mainly used as a working animal for riding and pack transport, as well as for dairy and meat production. Eye afflictions are common in donkeys, thus requiring a detailed study. A few studies had focused on the donkey's eye, and most of them had considered it, merely, a horse's eye. This study aimed to investigate the anatomy, histology, ultrastructure, and immunohistochemical features of the donkey's eye. The results were recorded and compared to those of horses in certain dimensions. Unlike horses, the donkey's eye is more circular in the contour of the cornea, has smaller lenticular thickness, and has longer anterior and vitreous chambers. Positive immunoreactivity to acidic fibroblast growth factor in the basal cell layers of the cornea was observed, indicating their role in cell differentiation and the renewal of the epithelium. Moreover, the corneal keratocytes expressed angiotensin-converting enzyme, which plays a role in corneal homeostasis and wound healing. Additionally, telocytes, hyalocytes, and other immune cells were observed within the iris and ciliary processes. Hence, this work is an updated detailed study of the morphology and ultrastructure of the donkey's eye and reveals some similarities and dissimilarities to the horse's eyes, which should be considered in clinical practice.

Hypoxia Response Element-Directed Expression of aFGF in Neural Stem Cells Promotes the Recovery of Spinal Cord Injury and Attenuates SCI-Induced Apoptosis.

Reducing neuronal death after spinal cord injury (SCI) is considered to be an important strategy for the renovation of SCI. Studies have shown that, as an important regulator of the development and maintenance of neural structure, acidic fibroblast growth factor (aFGF) has the role of tissue protection and is considered to be an effective drug for the treatment of SCI. Neural stem cells (NSCs) are rendered with the remarkable characteristics to self-replace and differentiate into a variety of cells, so it is promising to be used in cell transplantation therapy. Based on the facts above, our main aim of this research is to explore the role of NSCs expressing aFGF meditated by five hypoxia-responsive elements (5HRE) in the treatment of SCI by constructing AAV–5HRE–aFGF–NSCs and transplanting it into the area of SCI. Our research results showed that AAV–5HRE–aFGF–NSCs can effectively restore the motor function of rats with SCI. This was accomplished by inhibiting the expression of caspase 12/caspase 3 pathway, EIF2α–CHOP pathway, and GRP78 protein to inhibit apoptosis.

Acidic fibroblast growth factor attenuates type 2 diabetes-induced demyelination via suppressing oxidative stress damage

Prolonged type 2 diabetes mellitus (T2DM) produces a common complication, peripheral neuropathy, which is accompanied by nerve fiber disorder, axon atrophy, and demyelination. Growing evidence has characterized the beneficial effects of acidic fibroblast growth factor (aFGF) and shown that it relieves hyperglycemia, increases insulin sensitivity, and ameliorates neuropathic impairment. However, there is scarce evidence on the role of aFGF on remodeling of aberrant myelin under hyperglycemia condition. Presently, we observed that the expression of aFGF was rapidly decreased in a db/db T2DM mouse model. Administration of exogenous aFGF was sufficient to block acute demyelination and nerve fiber disorganization. Furthermore, this strong anti-demyelinating effect was most likely dominated by an aFGF-mediated increase of Schwann cell (SC) proliferation and migration as well as suppression of its apoptosis. Mechanistically, the beneficial biological effects of aFGF on SC behavior and abnormal myelin morphology were likely due to the inhibition of hyperglycemia-induced oxidative stress activation, which was most likely activated by kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid-derived-like 2 (Nrf2) signaling. Thus, this evidence indicates that aFGF is a promising protective agent for relieving myelin pathology through countering oxidative stress signaling cascades under diabetic conditions.

Acid fibroblast growth factor facilitates the progression of atherosclerotic plaques regardless of alterations in serum lipid expression levels in HFD‑fed ApoE‑/‑ mice.

Atherosclerosis is recognized at present as a chronic metabolic disease of the arteries that leads to multifocal plaque development. Previous studies have reported that acid fibroblast growth factor (aFGF) is a critical therapeutic regulator in numerous chronic metabolic disorders. However, there is currently no direct evidence indicating whether aFGF serves a therapeutic role in atherosclerosis. In the present study, the role of aFGF in atherosclerotic lesion development was investigated by examining high‑fat diet (HFD)‑fed apolipoprotein E (ApoE)‑/‑ mice and parenteral administration of aFGF. Increased expression of aFGF and peroxisome proliferator‑activated receptorα (PPARα) was observed during atherosclerotic lesion development. The parenteral delivery of aFGF facilitated the progression of atherosclerosis without altering serum lipid expression levels in HFD‑fed ApoE‑/‑ mice. Furthermore, it was demonstrated that aFGF increased the expression of PPARα and inflammatory cytokines. The present results provided evidence that aFGF accelerates the progression of atherosclerosis and suggested that aFGF may be a potential therapeutic target for the prevention of atherosclerosis development.

Study on human aFGF fusion gene transformation with soybean 24 kDa oleosin and expression in safflower

To investigate the expression of acidic fibroblast growth factor (aFGF) in transgenic safflower and lay the foundation for the use of the plant bioreactor large-scale production aFGF. The haFGF gene was transformed into plant preference of the aFGF sequence as a basis for design of primers, plant preferences aFGF gene sequences was amplified by PCR. The vegetable body expression vector was constructed by using digested connection method and then transferred to Agrobacterium tumefaciens EHA105 by the freeze-thaw method. It transferred to safflowers by agrobacterium-mediated transformation method, and identified by PCR, southern blot and RT-PCR. The full-length aFGF gene sequences were amplified through PCR and constructed into plant expression vector with soybean oleosin and promoter, and transformed into safflower. Three independently transformed safflower plant units with point insertion were successfully obtained, which showed the same size of aFGF expression at the transcriptional level. The plant oil body expression vectors were successfully constructed, and the optimal condition for genetic transformation was selected. The transgenic safflower plants were obtained.

Transient expression of acidic fibroblast growth factor in pea (Pisum sativum L.) plants

Nowadays, there are many therapeutic proteins produced in different host plants in transient easy to perform, short production cycle, efficient and inexpensive. In this study, the modified pea early browning virus (PEBV) vector containing GFP and acidic fibroblast growth factor (aFGF) was introduced into pea plants by leave injection. GFP expression was first observed in the treated leaves 8 to 10 days post-inoculation (dpi) and reached to the highest accumulation in both leaves and stems in 12 to 14 dpi. We suggested that 12 to 14 dpi were the best harvesting time for foreign proteins. The aFGF expression in pea plants has also been confirmed by Western blot. Key words : Pea plants, acidic fibroblast growth factor, leave injection, plant bioreactor.

Acidic Fibroblast Growth Factor (FGF) Potentiates Glial-mediated Neurotoxicity by Activating FGFR2 IIIb Protein

Previous studies indicate that astrocytes are the brain cells that express acidic fibroblast growth factor (aFGF) and that the expression is increased upon activation. However, there has been no study investigating the significance of this phenomenon. Here we report that aFGF treatment of IFNγ-stimulated human astrocytes, and LPS/IFNγ-stimulated human microglia, enhances their secretion of inflammatory cytokines and other materials toxic to human neuroblastoma SH-SY5Y cells. The mechanism of aFGF enhancement involves stimulation of the receptor FGFR2 IIIb. We show by RT-PCR that this receptor, but not other FGF receptors, is robustly expressed by astrocytes and microglia. We establish by Western blotting, and immunohistochemistry on postmortem human brain tissue that the FGFR2 IIIb protein is expressed by both of these glial cell types. We blocked the inflammatory stimulant action of aFGF by transfecting microglia and astrocytes with a small inhibitory RNA (siRNA) to FGFR2 IIIb as well as by removal of aFGF using an anti-aFGF antibody. Treatment with bFGF in combination with the stimulants was without effect, but together with aFGF, it partially counteracted the action of aFGF, indicating that it may be a weak antagonist of FGFR2 IIIb. The inflammatory effect was also attenuated by treatment with inhibitors of protein kinase C, Src tyrosine kinase, and MEK-1/2 indicating the involvement of these intracellular pathways. Our data suggest that inhibition of expression or release of aFGF could have therapeutic potential by inhibiting inflammation in neurodegenerative diseases such as Alzheimer disease where many neuroinflammatory molecules are prominently expressed.

Adeno‐associated virus‐mediated human acidic fibroblast growth factor expression promotes functional recovery of spinal cord–contused rats

Following spinal cord injury, the delivery of neurotrophic factors to the injured spinal cord has been shown to promote axonal regeneration and functional recovery. In previous studies, we showed that acidic fibroblast growth factor (aFGF) is a potent neurotrophic factor that promotes the regeneration of axotomized spinal cord or dorsal root ganglion neurones. We constructed a recombinant adeno-associated virus (AAV) vector to express human aFGF and evaluated aFGF expression and function in AAV-aFGF-infected PC12 cells. We analyzed AAV-green fluorescent protein (GFP) tropism and AAV-mediated aFGF expression in contused spinal cords. Animals received behavioural testing to evaluate the functional recovery. Overexpression of aFGF was shown in AAV-aFGF-infected PC12 cells in a dose-dependent manner. Concurrently, neurite extension and cell number were significantly increased in AAV-aFGF infected cells. AAV-mediated GFP expression persisted for at least 5 weeks in contused spinal cords, and the most prominently transduced cells were neurones. Contusive injury reduced endogenous aFGF expression in spinal cords. Overexpression of aFGF was demonstrated in AAV-aFGF transduced spinal cords compared to AAV-GFP transduced spinal cords at 3 and 14 days post-injury. Evaluation of motor function revealed that the improvement of AAV-aFGF-treated rats was prominent. Both AAV-aFGF- and recombinant human aFGF-treated rats revealed significantly better recovery at 5 weeks post-injury, compared to vehicle- and AAV-GFP-treated rats. These data suggest that supplement of aFGF improve the functional recovery of spinal cord-contused rats and that AAV-aFGF-mediated gene transfer could be a clinically feasible therapeutic approach for patients after nervous system injuries.

Evaluation of aFGF/bFGF and FGF Signaling Pathway in the Wall of Varicose Veins

Extensive extracellular matrix remodeling of the vein wall is involved in varicose veins pathogenesis. The process is controlled by numerous factors, including peptide growth factors. The aim of the study was to evaluate acidic (aFGF) and basic (bFGF) fibroblast growth factors, their receptor (FGFR) and the MAP kinase pathway (ERK 1/2) in the wall of varicose and varicose veins complicated by thrombophlebitis, when compared to normal ones. Segments of normal, varicose, and varicose veins complicated by thrombophlebitis were collected during varicose veins surgery in 17 patients. Expression and content of aFGF and bFGF were evaluated with Western blot and enzyme-linked immunosorbent assay (ELISA) methods, respectively, whereas RT-PCR was employed to assess mRNA level of growth factors. Expression of FGFR and ERK 1/2 was examined with Western blot method. Increased aFGF expression and content were accompanied by increased aFGF mRNA level in the wall of varicose veins. Furthermore, alternatively spliced aFGF mRNA was shown in varicose veins complicated by thrombophlebitis. Expression, content, and mRNA level of bFGF were comparable in the investigated material. FGFR and ERK 1/2 expression was demonstrated in the wall of diseased veins, however, without any significant differences in comparison with the wall of normal veins. Overexpressed aFGF in the wall of varicose veins via FGFR and the MAP kinase pathway may influence expression of enzymes involved in extracellular matrix metabolism and play a role in vein wall remodeling, as well as in the disease pathogenesis.

Co-expression of aFGF and FGFR-1 is predictive of a poor prognosis in patients with esophageal squamous cell carcinoma

Overexpression of aFGF, bFGF and FGFR-1 has been reported in various cancers, and it has been suggested that it may be a poor prognostic factor in cases with solid tumors. Therefore, we attempted to determine whether overexpression of aFGF, bFGF and FGFR-1 might also be a poor prognostic factor in patients with esophageal squamous cell carcinoma, and examined the expression of aFGF, bFGF and FGFR-1 in esophageal cancer tissue specimens to clarify their clinical significance. Seventy-nine patients with squamous cell carcinoma of the esophagus who underwent resection at the Department of Surgery, Keio University Hospital, were enrolled as the subjects of this study. None of the patients had received any previous treatment. Formalin-fixed and paraffin-embedded sections of esophageal cancer tissue were stained by immunohistochemical methods and examined for expression of the angiogenetic factors and their receptors, and also to determine the microvascular density (MVD). We examined the correlations between the expression of aFGF, bFGF and FGFR-1, and the MVD, clinicopathological background factors and survival of the patients by conducting statistical analyses of the data. The results revealed that positive aFGF expression was associated with a larger tumor area (p=0.009), and co-expression of both aFGF and FGFR-1 was associated with a larger tumor area (p=0.01) and poorer prognosis (p=0.04). There were positive correlations between the expression of aFGF and FGFR-1 (p<0.0001), and between those of bFGF and FGFR-1 (p=0.04). aFGF may promote proliferation of esophageal cancer cells in an angiogenesis-independent and autocrine manner, and may contribute to rapid growth of esophageal cancer on recurrence after esophageal resection.

Expression of Basic Fibroblast Growth Factor Correlates with Resistance to Paclitaxel in Human Patient Tumors

Preclinical results indicate acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) present in solid tumors as a cause of broad-spectrum chemoresistance, whereas earlier clinical studies suggest that bFGF expression is associated with opposing outcomes in patients. We investigated the relationship between FGF expression and paclitaxel activity in tumors from bladder, breast, head and neck, ovarian, and prostate cancer patients. Tumors (n = 96) were maintained in three-dimensional histocultures, retaining tumor-stromal interaction. Bladder tumors were treated with paclitaxel for 2 h, and the other tumors for 24 h. Antiproliferative and proapoptotic effects of paclitaxel were quantified and correlated with expression of aFGF, bFGF, P-glycoprotein (Pgp), p53, and bcl-2. Fifty-one percent (49/96) and 63% (61/96) of tumors showed aFGF and bFGF staining, respectively. aFGF expression was positively correlated with tumor stage (p < 0.01), and bFGF expression with tumor grade and Pgp expression (p < 0.05). Paclitaxel inhibited antiproliferation in 86% of tumors (83/96), with an average inhibition of 46 +/- 19% (mean +/- SD) in the responding tumors. Paclitaxel also induced apoptosis in 96% of tumors (92/96), with an average apoptotic index of 12 +/- 7% in the responding tumors. aFGF expression did not correlate with tumor sensitivity to paclitaxel, whereas bFGF expression showed an inverse correlation (p < 0.01). bFGF expression was a stronger predictor of paclitaxel resistance compared to Pgp, p53, or Bcl-2. These results support a role of bFGF in paclitaxel resistance in human patient tumors.

Expression of acidic fibroblast growth factor and basic fibroblast growth factor in nasal polyps

Conclusion. Up-regulated expression of acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) in nasal polyps may be related to epithelial proliferation and neoangiogenesis associated with nasal polyp growth. Background and objectives. aFGF and bFGF are polypeptides that effect mitogenesis, neoangiogenesis and tissue repair. The purpose of this study was to investigate the expression of aFGF and bFGF at both the mRNA and protein levels in nasal polyps. Materials and methods. Tissue samples of nasal polyp and inferior turbinate mucosae were obtained. Reverse transcriptase (RT)-PCR, in situ hybridization, and Western blotting for aFGF and bFGF were performed in nasal polyp and nasal inferior turbinate. Results. RT-PCR showed 50% aFGF and 29% bFGF expression positivity in 14 nasal polyps; however, 13 turbinates revealed no PCR products. aFGF and bFGF expression was localized to some inflammatory cells of nasal polyps by in situ hybridization. Western blotting identified aFGF and bFGF molecular masses of 18 kDa and 24 kDa, respectively, in nasal polyps, and these levels were higher than those observed in nasal turbinates. aFGF and bFGF proteins were also localized in some inflammatory cells of nasal polyps by immunostaining.

Elevated expression of TGF-beta1 in head and neck cancer-associated fibroblasts.

Head and neck cancers are characterized by a vigorous desmoplastic response, but the contribution of stromal-derived growth factors to the tumor microenvironment is poorly understood. We evaluated the expression of stromal growth factor expression in head and neck squamous cell carcinoma (HNSCC) in normal and tumor-associated stromal cells. Stromal tissue was isolated from epithelial cells with laser capture microdissection (LCMD) and analyzed by cDNA array for the expression of TGFalpha, TGF-beta1, HGF, PDGF-alpha, IGFII, bFGF, aFGF, VEGFC, and VEGF. Primary fibroblasts were isolated in vitro from HNSCC tumors, adjacent histologically normal mucosa, and skin in vitro. Fibroblast populations were assessed for TGF-beta1 expression by ELISA and luciferase reporter assay to assess protein expression. We identified TGF-beta1 and IGFII overexpression in normal and tumor-associated stromal cells; however, only TGF-beta1 was significantly overexpressed (3.4-fold) in tumor-associated stroma. Assessment of carcinoma-associated fibroblasts (CAFs), normal dermal fibroblasts (NDFs), and normal mucosal fibroblasts (NMFs) in propagated fibroblasts demonstrated persistently elevated levels of TGF-beta1 in CAFs compared to NMF and NDF populations. Elevated levels of TGF-beta1 were identified in the stromal compartment of HNSCC tumors compared to normal mucosa by immunohistochemical analysis. These results suggest that TGF-beta1 mRNA and protein is specifically upregulated in CAFs in vitro and in vivo.

Infection of recombinant adenovirus expressing acidic fibroblasts growth factor enhances rabbit corneal endothelium proliferation

To transfer the gene encoding mammalian aFGF to rabbit corneal endothelial cell and determine transfection efficiency and the effect of Ad-aFGF on proliferation of RCEC. Replication-defective adenovirus was used to deliver the LacZ reporter gene to RCEC to determine transfection efficiency by X-gal staining. A cDNA encoding mammalian aFGF was cloned into an adenoviral vector that was used to transfect RCEC. The expression of aFGF gene mRNA and protein were demonstrated by Reverse transcription PCR and Western blot respectively. The effect of Ad-aFGF on proliferation of RCEC was determined by MTT assay. RT-PCR and Western blot from RCEC infected with Ad-aFGF for 48 h detected a specific cDNA amplification and protein expression of aFGF gene, and no positive result in control cells. Consistently, RCEC infected by MOI 20 of Ad-aFGF demonstrated an enhanced RCEC proliferation compared to controls (F = 217.107, P < 0.05). Adenoviral-mediated expression of aFGF can stimulate the proliferation of RCEC.

Identification of Ribosome-binding Protein p34 as an Intracellular Protein That Binds Acidic Fibroblast Growth Factor

With the aim of identifying new intracellular binding partners for acidic fibroblast growth factor (aFGF), proteins from U2OS human osteosarcoma cells were adsorbed to immobilized aFGF. One of the adsorbed proteins is a member of the leucine-rich repeat protein family termed ribosome-binding protein p34 (p34). This protein has previously been localized to endoplasmic reticulum membranes and is thought to span the membrane with the N terminus on the cytosolic side. Confocal microscopy of cells transfected with Myc-p34 confirmed the endoplasmic reticulum localization, and Northern blotting determined p34 mRNA to be present in a multitude of different tissues. Cross-linking experiments indicated that the protein is present in the cell as a dimer. In vitro translated p34 was found to interact with maltose-binding protein-aFGF through its cytosolic coiled-coil domain. The interaction between aFGF and p34 was further characterized by surface plasmon resonance, giving a K(D) of 1.4 +/- 0.3 microm. Even though p34 interacted with mitogenic aFGF, it bound poorly to the non-mitogenic aFGF(K132E) mutant, indicating a possible involvement of p34 in intracellular signaling by aFGF.

Effects of IL6 and IL1β on aFGF expression and excitotoxicity in NT2N cells

The interleukin-1β (IL1β) and interleukin-6 (IL6) have pro-inflammatory and neuroprotective functions and are elevated in many diseases of the brain. Here, mechanisms and effects of IL1β and IL6 on neuronal survival after excitatory stimulation were investigated in vitro. IL6 upregulated the expression of the neuroprotective acidic fibroblast growth factor (aFGF) and reduced the glutamate-induced cytotoxicity. IL1β treatment amplified the excitotoxic effects after 24 h, but longer treatment with IL1β stimulated the neuronal release of IL6 resulting in increased levels of aFGF and a decreased excitotoxicity. These data suggest that (1) IL6 exerts protective functions by upregulating the expression of aFGF and (2) the IL6/IL1β balance in the brain may regulate neuronal survival during neuropathological processes.

Locally reduced levels of acidic FGF lead to decreased expression of 28-kda calbindin and contribute to the selective vulnerability of the neurons in the entorhinal cortex in Alzheimer's disease.

Recent studies demonstrate that a disturbed calcium-homeostasis leading to increased susceptibility to excitotoxic triggers plays a major role in the neurodegenerative process initiating in layer 2 of the entorhinal cortex (EC2) during Alzheimer's disease (AD). Thus, proteins binding free Ca++ (i.e. calbindin) and factors regulating these proteins are of great importance for the neuroprotective-neurotoxic balance in the affected brain regions. In the present combined human and in vitro study evidence is provided that altered levels of the acidic fibroblast growth factor (aFGF) and calbindin expression are concomitantly present in EC2 neurons and have interactive effects. A dramatic loss of aFGF- and calbindin-labeled EC2 neurons was found. Further analysis of the surviving EC2 neurons revealed a strong immunoreactivity to calbindin and aFGF. In vitro experiments show that aFGF regulates calbindin expression, because treatment of differentiating neurons with recombinant aFGF increases calbindin expression in a time-dependent fashion. The data imply that a reduced expression of aFGF in EC2 neurons of AD brains leads to lower levels of calbindin resulting in decreased neuroprotective capacity.

Development of Normal and Injury-induced Gene Expression of aFGF, bFGF, CNTF, BDNF, GFAP and IGF-I in the Rat Retina

Focal mechanical injury to the retina substantially increases basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF) mRNA expression, accompanied by a transient increase in FGFR-1 mRNA, and this response is thought to protect photoreceptors near the injury site from inherited and light-induced retinal degenerations. We have now examined retinal gene expression of the principal survival factors involved in the response to injury in normal rats as a function of postnatal age both in normal and injured retinas. Sprague–Dawley rats were injured in one eye by needle incision through the retina at postnatal day (P) 10, 22, 35, 60, 90, 120 and 180. The other eye was uninjured and served as the control. Retinas were taken 1 day post-injury. Northern blot analysis was performed to determine the mRNA expression of the following factors and receptors: bFGF and acidic fibroblast growth factors (aFGF) and FGF receptor-1 (FGFR-1); CNTF and CNTF receptor alpha (CNTFR-alpha); brain-derived neurotrophic factor (BDNF) and its receptor trk B; and insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR); glial fibrillary acidic protein (GFAP) and opsin. In the uninjured control eyes, mRNA expression of most of the factors increased with postnatal age, with little expression at P10 and maximal expression levels reached at P22 (opsin), P35 (aFGF), P60 (BDNF) or P90 (bFGF, FGFR-1, CNTF and GFAP). In contrast, IGF-1 mRNA rapidly decreased from a high level of expression at P10 to about 55% of that level by P22, reaching a stable 45–50% of the P10 level at P35 and thereafter. The response to injury of bFGF, FGFR-1, CNTF and GFAP mRNAs increased with postnatal age. Unexpectedly, only minimal increases in bFGF, FGFR-1, CNTF and GFAP over those seen in the control eyes were observed before P35. Thereafter, the increase of bFGF mRNA after injury reached a maximum of three-fold at P60, maintained this level to P120, and slightly decreased to 2.5-fold by P180. Expression of FGFR-1 mRNA showed a maximum increase of 2.6-fold at P90. Expression of CNTF and GFAP mRNAs followed a time course similar to that of bFGF. Mechanical injury did not alter the mRNA levels of aFGF, BDNF, IGF-I, and receptors, CNTFR-alpha, trk B and IGF-IR. These data show that the response to injury is minimal at early postnatal ages but increases with age and peaks at P60–90 for most potential survival factors.

Enhancing effects of fibroblast growth factor on the proliferation of salivary gland carcinoma cells and salivary gland carcinogenesis

The proliferation of mouse submandibular gland carcinoma YT-12 cells was stimulated by endothelial cell growth factor (ECGF)/bovine brain-derived acidic fibroblast growth factor (aFGF) and recombinant human aFGF. To determine whether aFGF was capable of modifying salivary gland carcinogenesis, the effect of brain-derived aFGF was examined in vivo. Mice in Groups 1 and 2 were injected with 9,10-dimethyl-1,2-benzanthracene (DMBA) into the left submandibular gland, and then Group 1 mice received bovine brain-derived aFGF and Group 2 mice received vehicle subcutaneously for 10 weeks. Group 3 and 4 mice received either bovine brain-derived aFGF or vehicle only. Sixteen weeks after the start of the experiment, the incidence of submandibular gland carcinomas in Group 1 was significantly greater than that in Group 2. Immunohistochemical study indicated that ducts in the normal submandibular glands and carcinomas showed positive staining with anti-aFGF antibody. Immunoblot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the expression of aFGF in these tissues. FGF receptor (FGFR)-1 and FGFR-4 were detectable in the mouse submandibular glands and carcinomas. These findings suggest that bovine brain-derived aFGF stimulates the proliferation of submandibular gland carcinoma cells and promotes mouse submandibular gland carcinogenesis.

Expression of acidic fibroblast growth factor (aFGF) and fibroblast growth factor receptor 4 (FGFR4) in breast fibroadenomas

Background/Aim—Fibroadenomas are benign tumours composed of both glandular and fibrous tissue. The mechanisms regulating the growth of these tumours and the relation between the stromal and epithelial cells are poorly...