Novel insights into the expression of CGB1 & 2 genes by epithelial cancer cell lines secreting ectopic free hCGβ

Article

Burczynska, B., Kobrouly, L., Butler, S., Naase, M. and Iles, R. 2014. Novel insights into the expression of CGB1 & 2 genes by epithelial cancer cell lines secreting ectopic free hCGβ. Anticancer Research. 34 (5), pp. 2239-2248.
TypeArticle
TitleNovel insights into the expression of CGB1 & 2 genes by epithelial cancer cell lines secreting ectopic free hCGβ
AuthorsBurczynska, B., Kobrouly, L., Butler, S., Naase, M. and Iles, R.
Abstract

BACKGROUND
Ectopic secretion of human chorionic gonadotrophin free beta (hCGβ) by epithelial cancer is associated with aggressive tumors which more readily metastasize, possibly by acting as an autocrine anti-apoptotic agent. hCGβ is encoded by six homologous CGB genes, with poorly-understood variable transcriptionally active expression profiles; CGB1 and CGB2 have always been considered pseudogenes. However, transcripts from CGB1 and -2 can be detected in placental, testicular and pituitary tissues. The expression and function of these genes in cancer is less well-known.
MATERIALS AND METHODS
Expression profiles of CGB genes in epithelial cancer cells by quantitative polymerase chain reaction (qPCR) were explored, along with the consequence of specific siRNA silencing of CGB1 and 2. Immunohistochemical and immunoassay techniques were used to detect the translation and secretion of hCGβ in these cells.
RESULTS
CGB1 and -2 gene transcripts were only detected in cells which secreted hCGβ. siRNA-mediated silencing of CGB1 and -2 transcripts significantly reduced secreted protein in concordance with a reduction in cell survival to a greater degree than that of other CGB genes.
CONCLUSION
CGB genes 1 and 2, previously considered as pseudogenes, are notably expressed by epithelial cancer cell lines. The transcription of these genes, but not other CGB genes, correlates with a functionally expressed protein and propensity for cancer growth.

Research GroupBiomarkers for Cancer group
Molecular Biology group
PublisherInternational Institute of Anticancer Research (IIAR)
JournalAnticancer Research
ISSN0250-7005
Electronic1791-7530
Publication dates
Online31 May 2014
Print31 May 2014
Publication process dates
Deposited12 Dec 2018
Accepted24 Mar 2014
Output statusPublished
Publisher's version
Copyright Statement

The attached document is the published version of an article published by International Institute of Anticancer Research (IIAR) in the journal Anticancer Research, 34 (5). pp. 2239-2248. Permission was granted, on the 01/09/2020, by IIAR to make the full text available in this repository.

Web address (URL)http://ar.iiarjournals.org/content/34/5/2239.long
LanguageEnglish
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Neven, P., Iles, R., Carter, P., Shepherd, J. and Chard, T. 1994. Diurnal variation of urinary "hCG beta subunit core fragment" production evaluated in patients with gynecological neoplasms. Clinical Chemistry. 40 (3), pp. 484-485.
Characterisation of the differential expression of marker antigens by normal and malignant endometrial epithelium
Chatzaki, E., Gallagher, C., Iles, R., Ind, T., Nouri, A., Bax, C. and Grudzinskas, J. 1994. Characterisation of the differential expression of marker antigens by normal and malignant endometrial epithelium. British journal of cancer. 69 (6), pp. 1010-1014.
Measurement of urinary beta core fragment of human chorionic gonadotrophin in women with vulvovaginal malignancy and its prognostic significance
Carter, P., Iles, R., Neven, P., Ind, T., Shepherd, J. and Chard, T. 1995. Measurement of urinary beta core fragment of human chorionic gonadotrophin in women with vulvovaginal malignancy and its prognostic significance. British journal of cancer. 71 (2), pp. 350-353.
The effects of beta-human chorionic gonadotrophin on the in vitro growth of bladder cancer cell lines
Gillott, D., Iles, R. and Chard, T. 1996. The effects of beta-human chorionic gonadotrophin on the in vitro growth of bladder cancer cell lines. British journal of cancer. 73 (3), pp. 323-326.
The temporary anatomical structures prominent in the first trimester may be fulfilling exchange functions assigned to the placenta in the second and third trimester
Docherty, S., Iles, R., Wathen, N. and Chard, T. 1996. The temporary anatomical structures prominent in the first trimester may be fulfilling exchange functions assigned to the placenta in the second and third trimester. Human Reproduction. 11 (6), pp. 1157-1161.
Prognostic significance of the bcl-2 apoptotic family of proteins in primary and recurrent cervical cancer
Crawford, R., Caldwell, C., Iles, R., Lowe, D., Shepherd, J. and Chard, T. 1998. Prognostic significance of the bcl-2 apoptotic family of proteins in primary and recurrent cervical cancer. British journal of cancer. 78 (2), pp. 210-214.
Concentrations of placental protein 14 in uterine flushings from infertile women: validation of the collection technique and method of expression of results
Hamilton, J., Iles, R., Gunn, L., Wilson, C., Lower, A., Chard, T. and Grudzinskas, J. 1998. Concentrations of placental protein 14 in uterine flushings from infertile women: validation of the collection technique and method of expression of results. Human Reproduction. 13 (12), pp. 3357-3362.
The beta-subunit of human chorionic gonadotrophin exists as a homodimer
Butler, S., Laidler, P., Porter, J., Kicman, A., Chard, T., Cowan, D. and Iles, R. 1999. The beta-subunit of human chorionic gonadotrophin exists as a homodimer. Journal of molecular endocrinology. 22, pp. 185-192.
Clinical and endocrinological changes after electro-acupuncture treatment in patients with osteoarthritis of the knee
Ahsin, S., Saleem, S., Bhatti, A., Aslam, M. and Iles, R. 2009. Clinical and endocrinological changes after electro-acupuncture treatment in patients with osteoarthritis of the knee. Pain. 147 (1-3), pp. 60-66. https://doi.org/10.1016/j.pain.2009.08.004
Capillary electrophoresis of human follicular fluid
Wen, S., Perrett, D., Patel, P., Li, N., Docherty, S., Tozer, A. and Iles, R. 2009. Capillary electrophoresis of human follicular fluid. Journal of Chromatography B. 877 (31), pp. 3946-3952. https://doi.org/10.1016/j.jchromb.2009.09.046
The role of glycosylation in regulating glycoprotein hormone free alpha subunit and free beta subunit combination in the extra-embryonic coelomic fluid of early pregnancy
Blithe, D. and Iles, R. 1995. The role of glycosylation in regulating glycoprotein hormone free alpha subunit and free beta subunit combination in the extra-embryonic coelomic fluid of early pregnancy. Endocrinology. 136 (3), pp. 903-910. https://doi.org/10.1210/en.136.3.903
Can biological markers improve the management of breast cancer patients?
Leake, R., Anderson, L., Dowsett, M., Iles, R., Nicholson, R., Robertson, J., Walker, R. and UKCCR Biomarker group 2000. Can biological markers improve the management of breast cancer patients? British journal of cancer. 82 (10), pp. 1625-1626. https://doi.org/10.1054/bjoc.2000.1159
Biological markers: maintaining standards
Leake, R., Anderson, L., Dowsett, M., Iles, R., Nicholson, R., Robertson, J., Walker, R. and UKCCCR Biomarker group 2000. Biological markers: maintaining standards. British journal of cancer. 82 (10), pp. 1627-1628. https://doi.org/10.1054/bjoc.2000.1158
Determination of the glycoforms of human chorionic gonadotropin b-core fragment by matrix-assisted laser desoption/ionisation time of flight mass spectrometry
Jacoby, E., Kicman, A., Laidler, P. and Iles, R. 2000. Determination of the glycoforms of human chorionic gonadotropin b-core fragment by matrix-assisted laser desoption/ionisation time of flight mass spectrometry. Clinical Chemistry. 46 (11), pp. 1796-1803.
Regulation of endometrial cancer cell growth by luteinising hormone (LH) and follicle stimulating hormone (FSH)
Davies, S., Bax, C., Chatzaki, E., Chard, T. and Iles, R. 2000. Regulation of endometrial cancer cell growth by luteinising hormone (LH) and follicle stimulating hormone (FSH). British journal of cancer. 83 (12), pp. 1730-1734. https://doi.org/10.1054/bjoc.2000.1507
The increase in bladder carcinoma cell population induced by the free beta subunit of human chorionic gonadotrophin is a result of an anti-apoptotic effect and not cell proliferation
Butler, S., Ikram, M., Mathieu, S. and Iles, R. 2000. The increase in bladder carcinoma cell population induced by the free beta subunit of human chorionic gonadotrophin is a result of an anti-apoptotic effect and not cell proliferation. British journal of cancer. 82 (9), pp. 1553-1556. https://doi.org/10.1054/bjoc.2000.1177
The analysis of human amniotic fluid using capillary electrophoresis.
Stewart, C., Iles, R. and Perrett, D. 2001. The analysis of human amniotic fluid using capillary electrophoresis. Electrophoresis. 22 (6), pp. 1136-1142. https://doi.org/10.1002/1522-2683()22:6<1136::AID-ELPS1136>3.0.CO;2-A
High concentrations of CA 125 in uterine flushings: influence of cause of infertility and menstrual cycle day.
Hamilton, J., Iles, R., Gunn, L., Wilson, C., Lower, A. and Grudzinskas, J. 2002. High concentrations of CA 125 in uterine flushings: influence of cause of infertility and menstrual cycle day. Gynecological Endocrinology.
Reduction of bladder cancer cell growth in response to hCGb CTP37 vaccinated mouse serum.
Butler, S., Staite, E. and Iles, R. 2003. Reduction of bladder cancer cell growth in response to hCGb CTP37 vaccinated mouse serum. Oncology research. 14 (2), pp. 93-100.
Identification of post-translational modifications resulting from LH beta polymorphisms by matrix-assisted laser desorption time-of-flight mass spectrometric analysis of pituitary LH beta core fragment
Jacoby, E., Kicman, A. and Iles, R. 2003. Identification of post-translational modifications resulting from LH beta polymorphisms by matrix-assisted laser desorption time-of-flight mass spectrometric analysis of pituitary LH beta core fragment. Journal of molecular endocrinology. 30 (2), pp. 239-252. https://doi.org/10.1677/jme.0.0300239
The recently identified homodimeric beta-beta subunit of human chorionic gonadotrophin (hCGbb) is no more biologically active than the free beta subunit (hCGb)
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