Abstract
Many tumors produce factors that affect cell-cycle and cell proliferation. In the present study we have analyzed the effect of a mammary-tumor extract injection on the mitotic activity of several organs in young male C3H/S mice previously standardized for circadian periodicity. One-half of the animals received an intraperitoneal EA21b tumor extract dose at 16:00 h, while the other half received saline. Animals were sacrificed on the following day at 08:00, 12:00 or 16:00 h. 4 h after receiving an injection of colchicine by the same route. Samples of duodenum, kidney, liver, and submaxillary gland were excised and processed for hematoxylin-eosin staining. Mitotic indices, expressed as the number of colchicine-arrested metaphases per 1,000 nuclei, were assessed in convoluted tubule epithelium, duodenal crypt enterocytes, hepatocytes and submaxillary gland ductal and acinar sialocytes. All values were expressed as mean ± SEM. Statistical analyses were performed by ANOVA, Bonferroni and Student’s t-tests. In contrast to the mitotic indices reductions observed in renal convoluted tubules cells and duodenal crypt enterocytes, neither the submaxillary gland nor the liver were found to contain cell types whose mitotic activity was affected by the tumor extract. We conclude that EA21b mammary carcinoma contains one or more factors that inhibit the proliferation of selected populations of normal cells.
Similar content being viewed by others
References
Badrán A.F., Moreno F.R. & Echave Llanos J.M. 1985a. Effect of tumour extracts on liver growth: hepatocarcinomas SS1H and SS1K. Com. Biol. 2: 143–149.
Badrán A.F., Moreno F.R. & Echave Llanos J.M. 1985b. Development of the effect of an indifferentiated tumour extract on sinusoidal litoral cells of young growing liver. Microsc. Electron. Biol. Celular 9: 13–21.
Barbeito C.G., Albarenque S.M., Reyna J.C., Flamini M.A., Andrés Laube P.F. & Badrán A.F. 2002a. Mitotic activity of the duodenal crypt enterocytes in mice transplanted with EA21a mammary carcinoma. Cell Biol. Int. 26: 123–125.
Barbeito C.G., Flamini M.A., García M.N., Andrés Laube P.F., Andrini L.B. & Badrán A.F. 2002b. Development of compensatory hepatic hyperplasia in mice carrying the hepatocellular carcinoma ES12a. J. Clin. Exp. Cancer Res. 21: 397–400.
Barbeito C.G., Garcia M.N., Savignone C.A., Catalano V.A., Badrán A.F., Flamini M.A & Moreno F.R. 1997. Actividad mitótica de los epitelios de epidermis, lengua, túbulos contorneados renales y conductos de la glándula submaxilar del ratón portador del tumor SS1K. Ciencias Morfológicas 3: 9–18.
Bjarnason G.A. & Jordan R. 2002. Rhythms in human gastrointestinal mucosa and skin. Chronobiol. Int. 19: 129–140.
Breitkopf K., Godoy P., Ciuclan L., Singer M.V. & Dooley, S. 2006. TGF-β/Smad signaling in the injured liver. Z. Gastroenterol. 44: 57–66.
Canela N., Orases M., Fucho R., Mateo F., Gutierrez R., Pineda-Lucena A., Bachs O. & Perez-Paya E. 2006. Identification of an hexapeptide that binds to a surface pocket in cyclin A and inhibits the catalytic activity of the complex cyclin-dependent kinase 2-cyclin A. J. Biol. Chem. 281: 35942–35953.
Catalano V.A., Barbeito C.G., Moreno F.R. & Badrán A.F. 1996. Análisis de la actividad mitótica de la corteza renal en ratones portadores del tumor EA21a. Ciencias Morfológicas 2: 3–14.
Echave Llanos J.M., Badrán A.F. & Moreno F.R. 1986. Inhibiting effect of a hepatoma extract on the mitotic rate of regenating liver. Virchows Arch. (Cell Pathol.) 51: 17–27.
Errecalde A.L. & Echave Llanos J.M. 1993. Effect of ES2 tumor extract and plasma of tumor bearing animals on the mitotic activity of enterocytes of young mice. J. Exp. Clin. Cancer Res. 12: 75–79.
Fausto N. 2000. Liver regeneration. J Hepatol. 32(Suppl 1): 19–31.
Flamini M.A., González N.V., Barbeito C.G., Badrán A.F. & Moreno F.R. 1996. Study on a tumoral factors stimulant of hepatocyte mitosis. Analecta Veterinaria 16: 14–16.
Geimer P. & Bade E.G. 1991. The epidermal growth factor-induced migration of rat liver epithelial cells is associated with a transient inhibition of DNA synthesis. J. Cell. Sci. 100: 349–355.
Huitfeldt H., Skarpen E., Lindeman B., Becher R., Thrane V. & Schwarze P.J. 1996. Differential distribution of met and epidermal growth factor receptor in normal and carcinogen-treated rat liver. Histochem. Cytochem. 44: 227–233.
Inda A.M., García A.L., Errecalde A.L. & Badrán A.F. 1997. Effect of tissue and plasma factors on kidney proliferation. Biocell 2: 13–18.
Jiang B., Zhang J.S., Du J., Urrutia R. & Barnard J. 2003. Growth inhibitory signalling by TGFβ is blocked in Ras-transformed intestinal epithelial cells at a post-receptor locus. Cell. Signal. 15: 699–708.
Malmgren R.A. 1956. Observations on a liver stimulant present in tumour tissues. Cancer Res. 16: 232–236.
Malmgren R.A. & Mills W. 1961. Studies of properties of the liver mitotic stimulant (LMS) in mouse tumor tissue. J. Nat. Cancer Inst. 26: 525–532.
Massague J. 1990. The transforming growth factor β family. Annu. Rev. Cell. Biol. 6: 597–641.
Masuhara M., Yasunaga M., Tanigawa K., Tamuta F., Yamashita S., Sakaida I. & Okita K. 1996. Expression of hepatocyte growth factor, transforming growth factor α and transforming growth factor β1 messenger RNA in various human liver diseases and correlation with hepatocyte proliferation. Hepatology 24: 323–329.
Moreno F.R., Badrán A.F. & Flamini M.A. 1992. Effect of tumor extracts on the liver proliferation in young mice. Com. Biol. 10: 336.
Opleta K., O’Loughlin E.V., Shaffer E.A., Hayden J., Hollemberg M. & Gall D.G. 1987. Effect of epidermal growth factor on growth and postnatal development of the rabbit liver. Am. J. Physiol. 253: 622–625.
Ottino A. & Echave Llanos J.M. 1990. Efecto inhibidor del extracto del hepatocarcinoma transplantado SS1K y del plasma de los portadores sobre la actividad mitótica de los hepatocitos y células litorales del hígado de ratón. Patología 28: 155–160.
Surur J.M., Catalano V.A., Flamini M.A. & Barbeito C.G. 2005. Effects of presence of tumors on the daily mitotic activity of mouse pars intermedia. Cell Biol. Int. 29: 173–175.
Wen H.S., Yin Y., Broussard S.R., McCusker R.H., Freund G.G., Dantzeri, R. & Kelley K.W. 2004. Tumor necrosis factor α inhibits cyclin A expression and retinoblastoma hyperphosphorylation triggered by insulin-like growth factor-I induction of new E2F-1 synthesis. J. Biol. Chem. 279: 7435–7446.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Flamini, M.A., González, N.V. & Barbeito, C.G. Antimitotic activity of EA21b mammary-carcinoma extract. Biologia 62, 238–242 (2007). https://doi.org/10.2478/s11756-007-0039-y
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.2478/s11756-007-0039-y