Skip to main content
NCBI home page
Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 1986 Jul;112(1):29–32. doi: 10.1007/BF00394935

Estrogen responsive creatine kinase in human breast cancer cells

G Scambia 1, V Natoli 2, P Benedetti Panici 1, G Sica 2,✉, S Mancuso 1
PMCID: PMC12253162  PMID: 3733865

Abstract

The brain type (BB) isoenzyme of creatine kinase (CK) is a very sensitive marker of estrogen action in rat uterus and in experimental mammary tumors. In order to detect useful markers for estrogen dependent human breast cancer cell proliferation we measured CK levels and isoenzyme composition in the CG5 cells, an estrogen supersensitive variant of the MCF-7 human breast cancer cell line.

Under basal conditions, CK-BB accounted for 10%–15% of total enzymatic activity, while the MM isoenzyme represented the overwhelming component. In cells cultured in the presence of 5% charcoal-treated fetal calf serum, physiological concentrations (0.1–1 nM) of estradiol increased CK-BB levels in a dose- and time-related fashion. The effect was specific for estrogens and was prevented by antiestrogens.

Our results show that CK-BB is estrogen regulated in the CG5 cells and suggest a possible role for this enzyme as an additional marker of the hormonal responsiveness of breast cancer.

Key words: Creatine kinase BB, Breast cancer, Estrogens

Footnotes

Recipient of an “Associazione Italiana per la Ricerca sul Cancro“ fellowship

References

  1. Allegra JC, Korat O, Do HMT, Lippman ME (1981) The regulation of progesterone receptor by 17-β estradiol and tamoxifen in the ZR-75-1 human breast cancer cell line in defined medium. J Recept Res 2:17–28 [DOI] [PubMed] [Google Scholar]
  2. Amroch D, Cox S, Shaer A, Malnick S, Chatsubi S, Hallowes R, Kaye AM (1984) Estrogen-responsive creatine kinase in normal and neoplastic human breast. In: Bresciani F, King RJB, Lippman ME, Namer M, Raynaud JP (eds) Hormones and cancer. Raven Press, New York, pp 663–641 [Google Scholar]
  3. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantity of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254 [DOI] [PubMed] [Google Scholar]
  4. Burke RE, Harris SC, McGuire WL (1978) Lactate dehydrogenase in estrogen-responsive human breast cancer cells. Cancer Res 38:2773–2776 [PubMed] [Google Scholar]
  5. Gorski J, Morgan MS (1967) Estrogen effects on uterine metabolism: reversal by inhibitors of protein synthesis. Biochem Biophys Acta 149:282–287 [DOI] [PubMed] [Google Scholar]
  6. Horwitz KB, McGuire WL (1978) Nuclear mechanisms of estrogen action. Effects of estradiol and anti-estrogen on estrogen receptors and nuclear receptor processing. J Biol Chem 253:223–228 [PubMed] [Google Scholar]
  7. Horwitz KB, McGuire WL, Pearson OH, Segaloff A (1975) Predicting response to endocrine therapy in human breast cancer: a hypothesis. Science 189:726–727 [DOI] [PubMed] [Google Scholar]
  8. Iacobelli S, Scambia G, Natoli V, Natoli C, Sica G (1984) Estrogen stimulates cell proliferation and the increase of a 52000 dalton glycoprotein in human breast cancer cells. J Steroid Biochem 20:747–752 [DOI] [PubMed] [Google Scholar]
  9. Ip M, Milholland RJ, Rosen F, Kim U (1979) Mammary cancer: selective action of the estrogen receptor complex. Science 203:361–363 [DOI] [PubMed] [Google Scholar]
  10. Kaye AM (1983) Enzyme induction by estrogen. J Steroid Biochem 19:33–40 [PubMed] [Google Scholar]
  11. Kaye AM, Reiss N, Shaer A, Sluyser M, Iacobelli S, Amroch D, Soffer Y (1981) Estrogen responsive creatine kinase in normal and neoplastic cells. J Steroid Biochem 15:69–75 [DOI] [PubMed] [Google Scholar]
  12. Kaye AM, Reiss NA, Somjen D (in press) Hormonal regulation of creatine kinase BB. In: Brautbar N (ed) Cellular bioenergetics and compartmentation. Plenum Publ. Corp., New York
  13. McGuire WL (1980) Steroid hormone receptor in breast cancer treatment strategy. Recent Prog Horm Res 36:135–156 [DOI] [PubMed] [Google Scholar]
  14. Namer M, Lalanne C, Baulieu EE (1980) Increase of progesterone receptor by tamoxifen as a normal challenge test in breast cancer. Cancer Res 40:1750–1752 [PubMed] [Google Scholar]
  15. Natoli C, Sica G, Natoli V, Serra A, Iacobelli S (1983) Two new estrogen supersensitive variants of MCF-7 human breast cancer cell line. Breast Cancer Res Treat 3:23–32 [DOI] [PubMed] [Google Scholar]
  16. Oliver IT (1955) A spectrophotometric method for the determination of creatine phosphokinase and myokinase. Biochem J 61:116–122 [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Reiss NA, Kaye AM (1981) Identification of the major component of the estrogen-induced protein of rat uterus as the BB isoenzyme of creatine kinase. J Biol Chem 256:5741–5749 [PubMed] [Google Scholar]
  18. Scambia G, Kaye AM, Iacobelli S (1984) Creatine kinase BB in normal, hyperplastic and neoplastic endometrium. J Steroid Biochem 20:797–798 [DOI] [PubMed] [Google Scholar]
  19. Scambia G, Benedetti Panici P, Sica G, Natoli V, Caruso A, Mancuso S (1986) Steroid hormone receptors and creatine kinase activity in human breast cancer. Ann NY Acad Sci (in press)
  20. Smith DE, Gorski J (1968) Estrogen control of uterine glucose metabolism. J Biol Chem 243:4169–4174 [PubMed] [Google Scholar]
  21. Somjen D, Kaye AM, Binderman I (1985) Hormonal regulation of creatine kinase BB in normal and transformed bone cells. In: Ornoy A, Arell A, Sela J (eds) Current advances in skeletogenesis. Elsevier Science Publishers, pp 85–90
  22. Walker MO, Kaye AM (1981) RNA for the rat uterine estrogen-induced protein. J Biol Chem 256:23–26 [PubMed] [Google Scholar]

Articles from Journal of Cancer Research and Clinical Oncology are provided here courtesy of Springer

RESOURCES