Estrogens, androgens, and EGF receptor expression in gastric carcinoma induced byN-methyl-N'-nitro-N-nitrosoguanidine

Digestive Diseases and Sciences - Tập 39 - Trang 635-640 - 1994
L. Polimeno1,2, G. Silecchia1,2, E. Spaziani1,2, A. Scucchi1,2, P. Dell'Aquila1,2, E. Ierardi1,2, A. Materia1,2, A. Giangaspero1,2, N. Basso1,2, A. Francavilla1,2
1Department of Gastroenterology, Cl. Med. I. Facoltà di Medicina e Chirurgia, University of Bari, Bari, Italy
2II Clinica Chirurgica and Department of Biopathology, University “La Sapienza”, Rome, Italy

Tóm tắt

Complex and conflicting relationships between epidermal growth factor (EGF), estrogens (E), androgens (A), and related receptors (EGF-R, E-R, A-R) have been reported in different biological situations associated with cell proliferation. There is also evidence that EGF and sex hormone receptors may be involved in normal and neoplastic growth of the gastrointestinal mucosa. In this study, we investigated the behavior of EGF receptors and sex hormone and related receptors, duringN-methyl-N'-nitro-N-nitrosoguanidine (NG) -induced gastric carcinogenesis in Sprague-Dawley male rats. Four groups of 15 rats each (10 NG-treated and five controls) were sacrificed after 1, 20, 30, and 40 weeks of treatment. Gastric tissue from each rat was processed for receptor status (number and affinity) and proliferative activity. A significant and progressive decrease of A-R and EGF-R was observed starting from the 20th week, while no change of E-R occurred throughout the experiment. Cell proliferation in the gastric mucosa of NG-treated rats increased after 30 weeks of treatment. These data indicate that NG treatment is able to modify the receptor status of gastric mucosa in rats.

Tài liệu tham khảo

Tokunaga A, Kojima N, Andoh T, et al: Hormone receptors in gastric cancer. Eur J Cancer Clin Oncol 19:687–689, 1983 Sica V, Nola F, Conti E, et al: Estradiol and progesterone receptors in malignant gastrointestinal tumors. Cancer Res 44:4670–4674, 1984 D'Istria MS, Gasano S, Catuogno F: Androgen and progesterone receptors in colonic and rectal cancers. Dis Colon Rectum 29:263–265, 1986 Alford TC, Do HM, Geelhoed GW, Tsangaris NT, Lippman ME: Steroid hormone receptors in human colon cancers. Cancer 43:980–984, 1979 Greenway B, Iqbal MJ, Johnson PJ, Williams R: Oestrogen receptor proteins in malignant and fetal pancreas. Br Med J 283:751–753, 1981 Francavilla A, Di Leo A, Polimeno L, Conte D, Barone M, Fanizza G, Chiumarulo C, Rizzo G, Rubino M: Nuclear and cytosolic estrogen receptors in human colon carcinoma and in surrounding noncancerous clonic tissue. Gastroenterology 93:1301–1306, 1987 Sujimura T, Fujimura S, Baba T: Tumor production in the glandular stomach and alimentary tract of the rat byN-methyl-N-nitro-N-nitrosoguanidine. Cancer Res 30:455, 1970 Saito T, Inokuchi K, Takayama S, et al: Sequential morphological changes inN-methyl-N-nitro-N-nitrosoguanidine carcinogenesis in the glandular stomach of rats. Natl Cancer Inst 44:769, 1970 Descheneer EE, Tamura K, Bralow SP: Sequential histopathology and cell kinetics changes in rat pyloric mucosa during gastric carcinogenesis induced byN-nitro-N-nitrosoguanidine. Natl Cancer Inst 63:171–177, 1979 Ohgaki H, Tomihari M, Sato S, Kleihues P, Sugimura T: Differential proliferative response of gastric mucosa during carcinogenesis induced byN-methyl-N-nitro-N-nitrosoguanidine in susceptible ACI rats, resistant Buffalo rats, and their hybrid F1 cross. Cancer Res 48:5275–5279, 1988 Silecchia G, Materia A, Spaziani E, et al: Sequential evaluation of gastric intraluminal prostaglandin E2 release acid secretion and DNA flow-cytometry inN-methyl-N-nitro-N-nitrosoguanidine gastric carcinogenesis in the rat. Cancer Lett 49:73–80, 1990 Johnson LR, Guthrie PD: Stimulation of rat oxintic gland mucosal growth by epidermal growth factor. Am J Physiol 238:45–49, 1980 Sainsbury JRC, Sherbet GV, Farndon JR, Harris AL: Epidermal growth factor receptors and oestrogen receptors in human breast cancer. Lancet 16:364–366, 1985 Francavilla A, Ove P, Polimeno L, Sciascia C, Coetzee M, Pellicci R, Todo S, Kam I, Starzl TE: Different response to epidermal growth factor of hepatocytes in cultures isolated from male or female rat liver: Inhibitor effect of estrogen on binding and mitogenic effect of epidermal growth factor. Gastroenterology 93:597–605, 1987 Nicholas V, Costrini MD, Beck R: Epidermal growth factors—urogastrone receptors in normal human liver and primary hepatoma. Cancer 51:2191–2196, 1983 Lowry OH, Rosebrogh NJ, Farr AL, Randall RJ: Protein measurement with the Folin-phenol reagent. J Biol Chem 193:265–275, 1951 Scatchard G: The attraction of protein for small molecules and ions. Ann NY Acad Sci 51:660–672, 1949 King WJ, Greene GL: Monoclonal antibodies localize oestrogen receptor in the nuclei of target cells. Nature 306:745–747, 1984 Greene GL: Estrogen and progesterone receptor measurements with monoclonal antibodies. Int J Biol Markers 3:57–59, 1988 Eagon PK, Fisher SE, Imhoff AF: Estrogen-binding proteins of male rat liver: influences of hormonal changes. Arch Biochem Biophys 201:486–499, 1980 Francavilla A, Eagon PK, Di Leo A: Regenerating rat liver: Correlations between estrogen receptor localization and DNA synthesis. Gastroenterology 86:1410–1416, 1984 Francavilla A, Eagon PK, Di Leo A, Polimeno L, Panella C, Aquilino AM, Ingrosso M, van Thiel DH, Starzl TE: Sex hormone related functions in regenerating male rat liver. Gastroenterology 91:1263–1270, 1986 Bannister P, Sheridan P, Losowsky MS: Identification and characterization of the human hepatic androgen receptor. Endocrinology 23:495–502, 1985 Kunze E, Schauer A, Eder M, Seefledtc I: Early sequential lesions during development of experimental gastric cancer with special reference to dysplasias. J Cancer Res Clin Oncol 95:247–264, 1979 Risio M, Coverlizza S, Ferrari A, Candelaresi GL, Rossini FP: Immunohistochemical study of epithelial cell proliferation in hyperplastic polyps, adenomas and adenocarcinomas of the large bowel. Gastroenterology 94:899–906, 1988 Herrman JB: Breast cancer and associated extramammary malignant neoplasm. Am J Surg 124:620–628, 1972 Howell MA: The association between colorectal cancer and breast cancer. J Chron Dis 29:243–249, 1976 Basso N, Materia A, Silecchia G, Spaziani E, Scucchi L, Di Stefano D, Mingazzini P, Favalli C, Garaci E: Time-related interference of misoprostol with experimental gastric cancer formation induced byN-methyl-N'-nitro-N-nitrosoguanidine in the rat. J Cancer Res Clin Oncol 118:441–446, 1992 Francavilla A, DiLeo A, Eagon PK, et al: Regenerating rat liver: Correlation between estrogen receptor localization and deoxyribonucleic acid synthesis. Gastroenterology 86:552–557, 1984 Earp HS, O'Keefe EJ: Epidermal growth factor receptor numbers decrease during rat liver regeneration. J Clin Invest 67:1580–1583, 1981