Subscribe to RSS
Download PDF
DOI: 10.1055/s-2001-14937
Effects of Androgens and Estrogens and Catechol and Methoxy-Estrogen Derivatives on Mitogen-Activated Protein Kinase (ERK1,2) Activity in SW-13 Human Adrenal Carcinoma Cells[1]
Publication History
Publication Date:
31 December 2001 (online)
We tested the effects of 17β-estradiol as well as its catechol- and methoxy-derivatives, two androgens (DHEA and testosterone), a glucocorticoid (cortisol), a mineralocorticoid (aldosterone), and progesterone on the activity of ERK1,2, a key component of the ERK/MAPK enzyme phosphorylation cascade, in SW-13 human adrenal carcinoma cells. After a 24-hour exposure SW-13 cells incubated with 10-5 M concentrations of 17β-estradiol, its 2-hydroxy or its 2-methoxy derivative, all had elevated ERK activities (196 %, 159 %, and 275 %, respectively) relative to control cells (p < 0.01). Incubation with testosterone resulted in 162 % of control ERK activity (p < 0.01), whereas incubation with the far weaker androgen DHEA or with cortisol, aldosterone, or progesterone had no significant effects. These findings suggest sex steroid-specific influences in the induction or activation of signal transduction pathways known to play a crucial role in cellular proliferation and differentiation.
Key words:
Adrenal Carcinoma - Steroids - MAPK - ERK
1 This work was supported by the U.S. Department of Veterans Affairs.
References
- 1 Shan J D, Porvari K, Ruokonen M, Karhu A, Launonen V, Hedberg P, Oikarinen J, Vihko P. Steroid-involved transcriptional regulation of human genes encoding prostatic acid phosphatase, prostate-specific antigen, and prostate-specific glandular kallikrein. Endocrinology. 1997; 138 3764-3770
- 2 Myers R B, Oelschlager D, Manne U, Coan P N, Weiss H, Grizzle W E. Androgenic regulation of growth factor and growth factor receptor expression in the CWR22 model of prostatic adenocarcinoma. Int J Cancer. 1999; 82 424-429
- 3 Bondy P K.
Disorders of the adrenal cortex. In: Williams Textbook of Endocrinology,. JD Wilson and DW Foster (eds.) . Philadelphia, PA; WB Saunders Company 1985: 816-890MissingFormLabel - 4 Gittes R F. Carcinoma of the prostate. New Engl J Med. 1991; 324 236-245
- 5 Stearn M E, McGarvey T. Prostate cancer, therapeutics, diagnostic and basic studies. Lab Invest. 1992; 67 540-552
- 6 Boring C C, Squires T S, Tong T. Cancer statistics. CA Cancer J Clin. 1993; 43 7-26
- 7 Craft N, Sawyers C L. Mechanistic concepts in androgen-dependence of prostate cancer. Cancer & Metastasis Rev. 1999; 17 421-427
- 8 Seger R, Krebs E G. The MAPK signaling cascade. FASEB J. 1995; 9 726-735
- 9 Neary J T. MAPK cascades in cell growth and death. News in Physiol Sci. 1997; 12 286-293
- 10 Neary J T, Kang Y, Bu Y, Yu E, Akong K, Peters C M. Mitogenic signaling by ATP P2Y purinergic receptors in astrocytes: involvement of a calcium-independent protein kinase C, extracellular signal regulated protein kinase pathway distinct from the phosphatidylinositol-specific phospholipase C, calcium pathway. J Neurosci. 1999; 19 4211-4220
- 11 Kyriakis J M, Avruch J. Sounding the Alarm: Protein kinase cascades activated by stress and inflamation. J Biol Chem. 1996; 271 24 313-24 316
- 12 Bonni A, Brunet A, West A E, Datta S R, Takasu M A, Greenberg M E. Cell survival promoted by the Ras-MAPK signalling pathway by transcription-dependent and independent mechanisms. Science. 1999; 286 1358-1362
- 13 Bhatt R R, Ferrell J E Jr. The protein kinase p90 Rsk as an essential mediator of cytostatic factor activity. Science. 1999; 286 1362-1365
- 14 Gross S D, Schwab M S, Lewellyn A L, Maller J L. Induction of metaphase arrest in cleaving Xenopus embryos by the protein kinase p90Rsk. Science. 1999; 286 1365-1367
- 15 Sivaraman V S, Wang H, Nuovo G J, Malbon C C. Hyperexpression of mitogen-activated protein kinase in human breast cancer. J Clin Invest. 1997; 99 1478-1483
- 16 Brown J W, Puppala K, Neary J T, Fishman L M. Mitogen-activated protein kinase (MAPK) activity in varying types of human pheochromocytomas. Proc Soc Expl Biol. 1998; Abstract A7 22
- 17 Migliaccio A, Di Domenico M, Castoria G, de Falco A, Bontempo P, Nola E, Auricchio F. Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells. EMBO J. 1996; 15 1292-1300
- 18 Nuedling S, Kahlert S, Loebbert K, Meyer R, Vetter H, Grohe C. Differential effects of 17beta-estradiol on mitogen-activated protein kinase pathways in rat carciomyocytes. FEBS Lett. 1999; 454 271-276
- 19 Singh M, Setalo G J r, Guan X, Warren M, Toran-Allerand C D. Estrogen-induced activation of mitogen-activated protein kinase in cerebral cortical explants; convergence of estrogen and neurotrophin signaling pathways. J Neurosci. 1999; 19 1179-1188
- 20 Zhu X, Li H, Liu J P, Funder J W. Androgen stimulates mitogen-activated protein kinase in human breast cancer cells. Mol Cell Endocrinol. 1999; 152 199-206
- 21 Nader S, Hickey R C, Sellin R, Samaan N A. Adrenal cortical carcinoma. A study of 77 cases. Cancer. 1983; 51 707-711
- 22 DePablos V PL, Martinez M P, Sanchez M V, Santana A C, Martinez-Martin J, Hernandez R J. An adrenal carcinoma producing androgens, estrogens, and cortisol. Anales de Medicina Interna. 1997; 14 190-192
- 23 Muthusethupathi M A, Vimala A, Jayakumar M, Rajendran S. Normotensive primary aldosteronism due to adrenocortical carcinoma. Nephron. 1998; 79 247-248
- 24 Brown J W, Fishman L M. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas. Brazilian J Med & Biol Res. 2000; 33 1235-1244
- 25 Ehrhart-Bornstein M, Hilbers U. Neuroendocrine properties of adrenocortical cells. Horm Metab Res. 1998; 30 436-439
- 26 Reincke M. Mutations in adrenocortical tumors. Horm Metab Res. 1998; 30 447-455
1 This work was supported by the U.S. Department of Veterans Affairs.
Dr. J. W. Brown
Adrenal Research (151)
V.A. Medical Center
1201 N.W. 16 St.
Miami, FL 33125
U.S.A.
Phone: Phone:+ 1 (305) 324-3195
Fax: Fax:+ 1 (305) 324-3126