Does HCG or HCG-beta play a role in breast cancer cell biology?

Article

Iles, R. and Butler, S. 2010. Does HCG or HCG-beta play a role in breast cancer cell biology? Tumour Biology. 31 (S39).
TypeArticle
TitleDoes HCG or HCG-beta play a role in breast cancer cell biology?
AuthorsIles, R. and Butler, S.
Abstract

Aim: hCG's involvement in breast cancer has been antithetical: the detection of ectopically expressed hCGbeta by breast tumors has been employed as a biomarker of
malignancy, and hCG has been proposed as a ligand vehicle for toxic drugs. However, it has also been proposed that hCG is a protective agent against the development of breast
cancer, leading some to advocate hCG administration to non-pregnant women as a prophylactic measure against cancer. We review the current literature to reconcile these differences.
Method: Literature review and analysis.
Results: Recent work has hCGbeta is involved in the angiogenesis, metastasis and immune escape that are central to cancer progression-are phenomena which clearly apply to breast cancer. Conversely, hCg has been shown to alter gene expression and malignant behaviour of breast cancer cells and a clinical trial is underway to see if the incidence of breast cancer is reduced in women who received exogenous hCG.
Conclusion: We propose that this apparent paradox is resolved if the free beta subunit of hCG produced by tumors acts as an autocrine anti-apoptotic and angiogenic growth factor, whilst intact heterodimeric hCG, as in pregnancy, is part of developmental signaling that initiates tissue differentiation (including breast ductal tissue development), and hence reduces the population of stem-like cells which are susceptible to oncogenic factors.

PublisherSpringer
JournalTumour Biology
ISSN1010-4283
Publication dates
PrintAug 2010
Publication process dates
Deposited27 Jun 2011
Output statusPublished
LanguageEnglish
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Butler, S. and Iles, R. 2004. The recently identified homodimeric beta-beta subunit of human chorionic gonadotrophin (hCGbb) is no more biologically active than the free beta subunit (hCGb). Tumor Biology. 25 (1-2), pp. 18-23. https://doi.org/10.1159/000077719
Serum amino-terminal propeptide of type 1 procollagen (P1NP) in prostate cancer: a potential predictor of bone metastases and prognosticator for disease progression and survival.
Thurairaja, R., Iles, R., Jefferson, K., McFarlane, J. and Persad, R. 2006. Serum amino-terminal propeptide of type 1 procollagen (P1NP) in prostate cancer: a potential predictor of bone metastases and prognosticator for disease progression and survival. Urologia internationalis. 76 (1), pp. 67-71.
Immunoassay detection of human chorionic gonadotrophin beta (hCGb) expression by prostate cancer is of no clinical significance
Otite, U., Baithun, S., Chinegwundon, F., Nargund, V. and Iles, R. 2006. Immunoassay detection of human chorionic gonadotrophin beta (hCGb) expression by prostate cancer is of no clinical significance. Tumor Biology. 27, pp. 181-186.
Gonadotropins and prostate cancer: revisited.
Thwaini, A., Naase, M., Chinegwundon, F., Baithun, S., Ghali, L., Shergill, I. and Iles, R. 2006. Gonadotropins and prostate cancer: revisited. Urologia internationalis. 77 (4), pp. 289-296. https://doi.org/10.1159/000096330
Ectopic hCGbeta expression by epithelial cancer: malignant behaviour, metastasis and inhibition of tumor cell apoptosis
Iles, R. 2007. Ectopic hCGbeta expression by epithelial cancer: malignant behaviour, metastasis and inhibition of tumor cell apoptosis. Molecular and Cellular Endocrinology. 260-26, pp. 264-270. https://doi.org/10.1016/j.mce.2006.02.019
An introduction to mass spectrometry based proteomics-detection and characterization of gonadotropins and related molecules
Kicman, A., Parkin, M. and Iles, R. 2007. An introduction to mass spectrometry based proteomics-detection and characterization of gonadotropins and related molecules. Molecular and Cellular Endocrinology. 260-26, pp. 212-227. https://doi.org/10.1016/j.mce.2006.02.022
Towards the development of an electrochemical biosensor for hCGβ detection
Kassanos, P., Iles, R., Bayford, R. and Demosthenous, A. 2008. Towards the development of an electrochemical biosensor for hCGβ detection. Physiological Measurement. 29 (6), pp. S241-S254. https://doi.org/10.1088/0967-3334/29/6/S21
The role of glycoprotein hormones in endometrial cancer. (in Part 7: Hormones & hormone receptor)
Bax, C., Davies, S., Chatzaki, E., Butler, S. and Iles, R. 2003. The role of glycoprotein hormones in endometrial cancer. (in Part 7: Hormones & hormone receptor). in: Nishida, M. and Kuramoto, H. (ed.) Cell and molecular biology of endometrial carcinoma. London Springer. pp. 195-206
Molecular cell biology and genetic disorders
Iles, R. 2009. Molecular cell biology and genetic disorders. in: Kumar, P. and Clark, M. (ed.) Kumar & Clark’s clinical medicine. Edinburgh Elsevier Saunders. pp. 19-52
Chapter 1: Basic sciences: the cell.
Iles, R. 2008. Chapter 1: Basic sciences: the cell. in: Nargund, V., Raghavan, D. and Sandler, H. (ed.) Urological oncology. London Springer. pp. 3-36
Human chorionic gonadotropin isoforms in the diagnosis of ectopic pregnancy
Iles, R., Borrelli, P., Butler, S. and Staite, E. 2003. Human chorionic gonadotropin isoforms in the diagnosis of ectopic pregnancy. Clinical Chemistry. 49 (12), pp. 2045-2049. https://doi.org/10.1373/clinchem.2003.022095
Enhanced affinity capture MALDI-TOF MS: orientation of an immunoglobulin G using recombinant protein G
Iles, R., Bansal, S., Jacoby, E., Neubert, H., Cowan, D. and Kicman, A. 2002. Enhanced affinity capture MALDI-TOF MS: orientation of an immunoglobulin G using recombinant protein G. Analytical Chemistry. 74 (15), pp. 3677-3683. https://doi.org/10.1021/ac025558z
Identification of placental transforming growth factor-beta and bikunin metabolites as contaminants of pharmaceutical human chorionic gonadotrophin preparations by proteomic techniques
Iles, R., Kicman, A., Malatos, S. and Neubert, H. 2005. Identification of placental transforming growth factor-beta and bikunin metabolites as contaminants of pharmaceutical human chorionic gonadotrophin preparations by proteomic techniques. Molecular and Cellular Proteomics. 4 (7), pp. 984-992. https://doi.org/10.1074/mcp.M500085-MCP200
Ectopic human chorionic gonadotropin beta secretion by epithelial tumors and human chorionic gonadotropin beta-induced apoptosis in Kaposi's sarcoma: is there a connection?
Iles, R. and Butler, S. 2003. Ectopic human chorionic gonadotropin beta secretion by epithelial tumors and human chorionic gonadotropin beta-induced apoptosis in Kaposi's sarcoma: is there a connection? Clinical Cancer Research. 9 (13), pp. 4666-4673.
Human granulosa-lutein cell in vitro production of progesterone, inhibin A, inhibin B, and activin A are dependent on follicular size and not the presence of the oocyte
Wen, S., Tozer, A., Li, D., Docherty, S., Al-Shawaf, T. and Iles, R. 2008. Human granulosa-lutein cell in vitro production of progesterone, inhibin A, inhibin B, and activin A are dependent on follicular size and not the presence of the oocyte. Fertility and Sterility. 89 (5), pp. 1406-1413. https://doi.org/10.1016/j.fertnstert.2007.03.086
Follicular fluid levels of inhibin A, inhibin B, and activin A levels reflect changes in follicle size but are not independent markers of the oocyte's ability to fertilize
Wen, S., Tozer, A., Butler, S., Bell, C., Docherty, S. and Iles, R. 2006. Follicular fluid levels of inhibin A, inhibin B, and activin A levels reflect changes in follicle size but are not independent markers of the oocyte's ability to fertilize. Fertility and Sterility. 85 (6), pp. 1723-1729. https://doi.org/10.1016/j.fertnstert.2005.11.058
The effects of 'coasting' on follicular fluid concentrations of vascular endothelial growth factor in women at risk of developing ovarian hyperstimulation syndrome
Tozer, A., Iles, R., Iammarrone, E., Gillott, C., Al-Shawaf, T. and Grudzinskas, J. 2004. The effects of 'coasting' on follicular fluid concentrations of vascular endothelial growth factor in women at risk of developing ovarian hyperstimulation syndrome. Human Reproduction. 19 (3), pp. 522-528. https://doi.org/10.1093/humrep/deh096
Characteristics of populations of granulosa cells from individual follicles in women undergoing 'coasting' during controlled ovarian stimulation (COS) for IVF
Tozer, A., Iles, R., Iammarrone, E., Gillott, C., Wen, S., Al-Shawaf, T. and Grudzinskas, J. 2004. Characteristics of populations of granulosa cells from individual follicles in women undergoing 'coasting' during controlled ovarian stimulation (COS) for IVF. Human Reproduction. 19 (11), pp. 2561-2568. https://doi.org/10.1093/humrep/deh487
The free monomeric beta subunit of human chorionic gonadotrophin (hCG beta) and the recently identified homodimeric beta-beta subunit (hCG beta beta) both haveautocrine growth effects
Butler, S. and Iles, R. 2004. The free monomeric beta subunit of human chorionic gonadotrophin (hCG beta) and the recently identified homodimeric beta-beta subunit (hCG beta beta) both haveautocrine growth effects. Tumor Biology. 25 (1-2), pp. 18-23. https://doi.org/10.1159/000077719
Cross-Reaction with luteinizing hormone ß-Core is responsible for the age-dependent increase of immunoreactive ß-Core fragment of human chorionic gonadotropin in women with nonmalignant conditions
Iles, R., Javid, M., Gunn, L. and Chard, T. 1999. Cross-Reaction with luteinizing hormone ß-Core is responsible for the age-dependent increase of immunoreactive ß-Core fragment of human chorionic gonadotropin in women with nonmalignant conditions. Clinical Chemistry. 45 (4), pp. 532-538. https://doi.org/10.1093/clinchem/45.4.532
The prognostic significance of beta human chorionic gonadotrophin and its metabolites in women with cervical carcinoma
Crawford, R., Iles, R., Carter, P., Caldwell, C., Shepherd, J. and Chard, T. 1998. The prognostic significance of beta human chorionic gonadotrophin and its metabolites in women with cervical carcinoma. Journal of Clinical Pathology. 51 (9), pp. 685-688. https://doi.org/10.1136/jcp.51.9.685
Serum placental-type alkaline phosphatase activity in women with squamous and glandular malignancies of the reproductive tract
Ind, T., Iles, R., Carter, P., Lowe, D., Shepherd, J., Hudson, C. and Chard, T. 1994. Serum placental-type alkaline phosphatase activity in women with squamous and glandular malignancies of the reproductive tract. Journal of Clinical Pathology. 47 (11), pp. 1035-1037. https://doi.org/10.1136/jcp.47.11.1035