Intracrinology and gastric cancer
AbstractOverall incidence of gastric cancer (GC) in most populations is approximately two times higher in men than women. Therefore, steroid hormones are suspect to play a role in gastric carcinogenesis. Large amounts of steroid hormones in postmenopausal women and older men are synthesized in peripheral tissues through enzymatic conversion of blood derived precursors into active estrogens and androgens in so called, intracrine mechanism. Moreover, abnormal expression of genes encoding steroidogenic enzymes was shown in numerous malignant tumors including GC. These abnormalities can be associated with deregulated production of steroid hormones in gastric tissue and thus affect the risk of GC. For that reason this short review aims to summarize the current knowledge about the expression of genes involved in metabolism of steroid hormones in normal and malignant gastric mucosa and thus, estimate the potential of these tissues to intracrine synthesis of steroid hormones. This findings could be useful in understanding the role of above mechanism in GC and could help to find therapeutic approaches in future.
Camargo MC, Goto Y, Zabaleta J, Morgan DR, Correa P, Rabkin CS. Sex hormones, hormonal interventions, and gastric cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2012;21(1):20–38.
Labrie F. Extragonadal synthesis of sex steroids: intracrinology. Ann Endocrinol (Paris). 2003;64(2):95–107.
Ueyama T, Shirasawa N, Numazawa M, Yamada K, Shelangouski M, Ito T, Tsuruo Y. Gastric parietal cells: potent endocrine role in secreting estrogen as a possible regulator of gastro-hepatic axis. Endocrinology. 2002;143(8):3162–70.
Le Goascogne C, Sananes N, Eychenne B, Gouézou M, Baulieu EE, Robel P. Androgen biosynthesis in the stomach: expression of cytochrome P450 17 alpha-hydroxylase/17,20-lyase messenger ribonucleic acid and protein, and metabolism of pregnenolone and progesterone by parietal cells of the rat gastric mucosa. Endocrinology. 1995;136(4):1744–52.
Sasano H, Suzuki T, Nakata T, Moriya T. New development in intracrinology of breast carcinoma. Breast Cancer. 2006;13(2):129–36.
Mungenast F, Thalhammer T. Estrogen biosynthesis and action in ovarian cancer. Front Endocrinol (Lausanne). 2014;5:192.
Frycz BA, Jagodziński PP. Expressions of genes encoding steroidogenic enzymes and their role in prostate carcinogenesis. JMS. 2014;83(1):73–80.
Drzewiecka H, Gałęcki B, Jarmołowska-Jurczyszyn D, Kluk A, Dyszkiewicz W, Jagodziński PP. Increased expression of 17-beta-hydroxysteroid dehydrogenase type 1 in non-small cell lung cancer. Lung Cancer. 2015;87(2):107–16.
Nakamura Y, Shimada N, Suzuki T, Imatani A, Sekine H, Ohara S et al. In situ androgen production in human gastric carcinoma--androgen synthesizing and metabolizing enzymes. Anticancer Res. 2006;26(3A):1935–9.
Frycz BA, Murawa D, Borejsza-Wysocki M, Marciniak R, Murawa P, Drews M, Jagodziński PP. Expression of 17ß-hydroxysteroid dehydrogenase type 2 is associated with some clinicopathological features in gastric cancer. Biomed Pharmacother. 2015;70:24–7.
Frycz BA, Murawa D, Borejsza-Wysocki M, Wichtowski M, Spychała A, Marciniak R et al. Transcript level of AKR1C3 is down-regulated in gastric cancer. Biochem Cell Biol. 2016;94(2):138–46.
Frycz BA, Murawa D, Borejsza-Wysocki M, Wichtowski M, Spychała A, Marciniak R et al. mRNA expression of selected genes encoding steroidogenic enzymes, steroid hormone receptors and their co-regulators in gastric cancer. Oncology Letters [ahead of published]
Brodie A, Njar V, Macedo LF, Vasaitis TS, Sabnis G. The Coffey Lecture: steroidogenic enzyme inhibitors and hormone dependent cancer. Urol Oncol. 2009;27(1):53–63.
Labrie C, Belanger A, Labrie F. Androgenic activity of dehydroepiandrosterone and androstenedione in the rat ventral prostate. Endocrinology. 1988;123(3):1412–7.
Suzuki M, Ishida H, Shiotsu Y, Nakata T, Akinaga S, Takashima S et al. Expression level of enzymes related to in situ estrogen synthesis and clinicopathological parameters in breast cancer patients. J Steroid Biochem Mol Biol. 2009;113(3–5):195–201.
Idkowiak J, Taylor AE, Subtil S, O'Neil DM, Vijzelaar R, Dias RP et al. Steroid Sulfatase Deficiency and Androgen Activation Before and After Puberty. J Clin Endocrinol Metab. 2016;101(6):2545–53.
Frycz BA, Murawa D, Wysocki-Borejsza M, Marciniak R, Murawa P, Drews M, Jagodziński PP. Expression of 17ß-hydroxysteroid dehydrogenase type 1 in gastric cancer. Biomed Pharmacother. 2013;67(7):651–7.
Dozmorov MG, Azzarello JT, Wren JD, Fung KM, Yang Q, Davis JS et al. Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: implications for prostate cancer progression. BMC Cancer. 2010;10:672.
Oduwole OO, Mäkinen JM, Isomaa VV, Karttunen TJ, Vihko PT. Sex steroid metabolism in human gastric mucosa: 17 beta-hydroxysteroid dehydrogenase type 2 in normal, inflamed and neoplastic gastric tissues. Anticancer Res. 2003;23(5A):3889–97.
Tian Y, Wan H, Lin Y, Xie X, Li Z, Tan G. Androgen receptor may be responsible for gender disparity in gastric cancer. Med Hypotheses. 2013;80(5):672–4.
Saitoh Y, Sasano H, Naganuma H, Ohtani H, Sasano N, Ohuchi A, Matsuno S. De novo expression of aromatase in gastric carcinoma. Light and electron microscopic immunohistochemical and immunoblot study. Pathol Res Pract. 1992;188(1–2):53–60.
Kobayashi H, Yoshida S, Sun YJ, Shirasawa N, Naito A. Postnatal development of gastric aromatase and portal venous estradiol-17ß levels in male rats. J Endocrinol. 2013;218(1):117–24.
Kobayashi H, Yoshida S, Sun YJ, Shirasawa N, Naito A. 17ß-Estradiol in the systemic circulation derives mainly from the parietal cells in cholestatic female rats. J Endocrinol Invest. 2016;39(4):389–400.
Ozawa M, Takahashi K, Akazawa KH, Takashima T, Nagata H, Doi H et al. PET of aromatase in gastric parietal cells using 11C-vorozole. J Nucl Med. 2011;52(12):1964–9.
Izawa M, Inoue M, Osaki M, Ito H, Harada T, Terakawa N, Ikeguchi M. Cytochrome P450 aromatase gene (CYP19) expression in gastric cancer. Gastric Cancer. 2008;11(2):103–10.