epidermal-growth-factor and Submandibular-Gland-Neoplasms

This study investigated whether epidermal growth factor (EGF) administration was capable of modifying salivary gland carcinogenesis. Two groups of mice were given 1 mg of 9,10-dimethyl-1,2-benzanthracene (DMBA) into the left submandibular gland, and then Group 1 mice received 2 microg of EGF and Group 2 mice received vehicle subcutaneously for 8 weeks. Mice in two other groups, 3 and 4, received either EGF or vehicle alone. Twelve weeks after the start of the experiment, the incidences of submandibular gland carcinomas in Groups 1 and 2 were 39% and 58%, respectively, although this difference was not statistically significant. Duct- and cyst-like structures and carcinomas in the left submandibular glands were weakly stained by anti-EGF receptor (EGFR) antibody. Immunoblot and reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed the expression of EGFR in the submandibular glands and carcinomas. However, EGFR was undetectable in YT cells that were derived from a submandibular gland undifferentiated carcinoma of a Group 2 mouse. These findings indicate that EGF does not promote tumor induction in mouse salivary gland carcinogenesis. This may be ascribed in part to the low expression level of EGFR in tumor cells.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma; Epidermal Growth Factor; ErbB Receptors; Female; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic; Immunoblotting; Incidence; Injections; Injections, Subcutaneous; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Mice, Nude; Neoplasm Transplantation; Pharmaceutical Vehicles; Polymerase Chain Reaction; Salivary Ducts; Submandibular Gland; Submandibular Gland Neoplasms; Tumor Cells, Cultured

To determine whether testosterone administration was capable of modifying salivary gland carcinogenesis, female mice were given 1 mg of 9,10-dimethyl-1,2-benzanthracene (DMBA) into the left submandibular gland and then Group 1 mice received 5 mg of testosterone propionate and Group 2 mice received vehicle, olive oil, subcutaneously for 8 weeks. Twelve weeks after the start of the experiment, the weight of the left submandibular gland of the Group 2 mice was greater than that of the Group 1 mice. The incidences of submandibular gland carcinoma in Groups 1 and 2 were 41% (12/29) and 57% (17/30), respectively. Epidermal growth factor (EGF) levels of the left submandibular gland were significantly higher in Group 1 as compared with Group 2. These findings indicate that testosterone increases the production of EGF in the DMBA-injected submandibular gland, but does not promote the development of submandibular gland carcinoma.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Animals; Carcinoma; Carcinoma, Squamous Cell; Epidermal Growth Factor; Female; Mice; Organ Size; Submandibular Gland; Submandibular Gland Neoplasms; Testosterone

The pattern of expression of the simian virus 40 (SV40) T antigen gene and resultant dysplasia were re-examined in a line of transgenic mice in which the T antigen gene was under the control of the SV40 early promoter. We found that T antigen expression in the kidney, and resulting dysplastic lesions, occurred exclusively in the distal convoluted tubules and the ascending limbs of Henle. Epidermal growth factor (EGF) expression in the kidney of normal mice was similarly immunolocalized. The correlation between high EGF immunoreactivity in normal mouse tissues and T antigen expression in the transgenic counterpart was also seen in the choroid plexus epithelium and in the submandibular glands of male mice. T antigen was not found in the submandibular gland of transgenic females. Similarly, EGF was only rarely detected in the normal female submandibular gland. In contrast to the correlation between T antigen expression in the transgenic mice and EGF expression in the corresponding tissues of the normal mice, within the dysplastic lesions of the transgenic mice EGF expression was severely diminished. Adenocarcinomas of the male submandibular gland from another line of transgenic mice that expresses the Int-1 transgene, showed similarly reduced levels of immunostaining for EGF. Thus, reduced expression of EGF might be a general feature of dysplasia and tumorigenesis in those tissues that normally express EGF.

Topics: Adenocarcinoma; Animals; Antigens, Viral, Tumor; Cattle; Choroid Plexus; Cricetinae; Epidermal Growth Factor; Female; Gene Expression Regulation, Neoplastic; Kidney; Kidney Tubules, Distal; Male; Mice; Mice, Transgenic; Proto-Oncogene Proteins; Simian virus 40; Submandibular Gland; Submandibular Gland Neoplasms; Wnt Proteins; Wnt1 Protein; Zebrafish Proteins

The phenotypic expression of the human epidermal growth factor (EGF) was investigated immunohistochemically in human foetal submandibular glands from the 5th to 10th month of gestation, adult normal submandibular glands and 48 cases of pleomorphic adenomas. In foetal submandibular glands, both the terminal buds and primary ducts at the intermediate stage of gestation were positive for EGF, and in particular, the outer layer cells of primary ducts showed strong EGF-immunoreactivity. EGF-positive cells decreased as the gestational stage advanced and only ductal cells were weakly positive for EGF at the terminal stage of gestation. In the adult normal submandibular gland, weak immunoreactivity for EGF was restricted to ductal cells. However, 41 (86%) of the 48 pleomorphic adenomas had EGF-positive cells which were distributed among the ductal, chondroid and myxoid portion. No EGF-immunoreactivity was detected in the solid portion of pleomorphic adenomas. These results suggest that EGF may play an important role in the growth and differentiation of foetal cells as well as the proliferation of tumour cells in pleomorphic adenomas.

Topics: Adenoma, Pleomorphic; Antibodies; Epidermal Growth Factor; Fetus; Humans; Immunohistochemistry; Phenotype; Salivary Gland Neoplasms; Submandibular Gland Neoplasms

The treatment of a human submandibular gland adenocarcinoma cell line (HSG cell line) for 48 h with triamcinolone acetonide (TA; 1-100 nmol/l) reduced the secretion of epidermal growth factor (EGF) in a closely related manner to a maximum of 66%. The reduction in the level of EGF secreted resulted in the suppression of DNA synthesis in the HSG cells to a similar extent. When the cells were incubated with TA and exogenous human EGF (hEGF), DNA synthesis was 1.7-fold higher than that without added hEGF. The removal of EGF by the addition of hEGF antibody reduced DNA synthesis in HSG cell cultures to the same extent as did TA. These results suggest that the growth inhibition of HSG cells by TA is due to the reduction in the amount of EGF secreted.

Topics: Adenocarcinoma; Cell Line; DNA, Neoplasm; Epidermal Growth Factor; Humans; Salivary Gland Neoplasms; Submandibular Gland Neoplasms; Triamcinolone Acetonide; Tumor Cells, Cultured

We applied immunohistochemical procedures to detect hEGF in salivary glands and pleomorphic adenomas of salivary-gland origin using a polyclonal hEGF antiserum and a monoclonal antibody against hEGF synthesized by applying the synthetic gene technique using Escherichia coli. In normal salivary glands, hEGF was mainly localized in the ductal system (i.e., intercalated, striated, and excretory ducts). The staining intensity and intracellular localization exhibited some variation depending on the fixative used. When a polyclonal hEGF antiserum was used for immunostaining, slight background staining was observed in sections prepared using the fixatives tested. Therefore, precise localization of hEGF was obtainable only in formalin-fixed sections using the monoclonal antibody against hEGF. In pleomorphic adenomas, positive hEGF staining was seen on the luminal side of tumors and in cells of ductal origin; no reactivity was present on the outer side of tumors or in cells of myoepithelial origin. Occasionally, long, spindle-shaped tumor cells and chondroidally changed tumor cells also exhibited positive staining for hEGF.

Topics: Adenoma; Antibodies, Monoclonal; Epidermal Growth Factor; Humans; Immune Sera; Immunodiffusion; Immunohistochemistry; Radioimmunoassay; Salivary Gland Neoplasms; Submandibular Gland; Submandibular Gland Neoplasms

Immunohistochemical identification of epidermal growth factor (EGF) is described in experimental carcinoma of the submandibular gland of mice given testosterone before sacrifice. EGF in the submandibular gland was confined to the granular convoluted tubule (GCT) cells, and its level was enhanced following testosterone injection. In the initial phase of carcinogenesis of the gland, degranulation of the GCT cells occurred as well as decreased EGF staining in the degranulated cells. In the testosterone-treated animals, changed GCT cells showed intense EGF deposition. Histological aspects during carcinogenesis in submandibular glands indicated duct-like structures, squamous metaplasia, and squamous cell types of carcinoma with different keratinization. Immunohistochemically detectable EGF was characterized by positive staining in pre-neoplastic or early neoplastic epithelial structures in testosterone-treated mice. However, tumour epithelia did not show any EGF reaction.

Topics: Animals; Carcinoma, Squamous Cell; Epidermal Growth Factor; Female; Histocytochemistry; Male; Mice; Mice, Inbred Strains; Salivary Gland Neoplasms; Submandibular Gland Neoplasms; Testosterone

Immunohistochemical demonstration of epidermal growth factor (EGF) and nerve growth factor (NGF) was made during chemical carcinogenesis in the mouse submandibular gland. The granular convoluted tubule cells in the normal male submandibular gland contained larger amounts of EGF and NGF than in the female. The initial phase and early stages in chemical carcinogenesis showed degranulation of the granular convoluted tubule cells with a marked decrease in EGF and NGF. Premalignant lesions such as duct-like structures and multicystic lesions showed variable staining for EGF and were usually negative for NGF. Material secreted into the luminal spaces revealed increased staining for EGF and NGF. Scattered tumor cells of the poorly differentiated squamous-cell carcinoma type and desquamated tumor cells contained abundant EGF, but not NGF. No positive reaction for EGF or NGF was found in the induced squamous-cell carcinoma cells.

Topics: Animals; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cytoplasmic Granules; Epidermal Growth Factor; Female; Male; Mice; Nerve Growth Factors; Salivary Gland Neoplasms; Submandibular Gland Neoplasms