<i>In Vivo</i>and<i>in Vitro</i>Production of Human Chorionic Gonadotropin and Alpha-Fetoprotein by a Virilizing Hepatoblastoma

Braunstein, Glenn D.; Bridson, William E.; Glass, Andrew G.; Hull, Edgar; McIntire, K. Robert

doi:10.1210/jcem-35-6-857

Cited by 62 publications

(17 citation statements)

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“…These kinds of properties suggest cooperative interaction between the protein that binds to the enhancer and a protein(s) that binds to specific downstream promoter elements in which the latter protein may not be expressed in all cell types. The results of the current study suggest that the CGa promoter is indeed very receptive to cAMP-REs and PMA-REs in Hep G-2 as well as JEG-3 cells, perhaps consistent with the frequently observed ectopic expression of CGa in liver carcinomas (28).…”

Section: Discussionsupporting

confidence: 88%

Cyclic AMP and phorbol ester-stimulated transcription mediated by similar DNA elements that bind distinct proteins.

Deutsch

Hoeffler

Jameson

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

177

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ABSTRACTcAMP and phorbol esters mediate cellular metabolism by the activation of distinct signal transduction pathways consisting of a cascade of sequential protein phosphorylations. An important consequence of the activation of these pathways is the stimulation of gene transcription by way of interactions of specific proteins with DNA control elements. The 8-base-pair (bp) DNA consensus sequence TGACGTCA [cAMP response element (cAMP-RE)] has been shown to confer cAMP responsivity on transcription from various promoters, and the closely related 7-bp consensus sequence TGA-(C or G)TCA [phorbol 12-myristate 13-acetate response element (PMA-RE)] lends transcriptional responsiveness to phorbol esters. In the JEG-3 placental cell line we find that several variants of the cAMP-REs fused to a gonadotropin a promoter chloramphenicol acetyltransferase reporter gene mediate responsiveness to cAMP but not to phorbol esters. The PMA-RE is responsive to phorbol esters but also imparts submaximal sensitivity to cAMP in the JEG-3 cells and in the Hep G2 hepatoma cell line. The transcriptional activities of cAMP-RE and PMA-RE are markedly influenced by the composition of the neighboring bases, but different sequences are permissive for the activity of the cAMP-RE versus the PMA-RE. The two signaling agents together display a supraadditive effect on reporter genes containing active PMA-REs but not cAMP-REs. Gel-mobility-shift and UV cross-linking analyses show that distinct proteins bind to the two control elements. One protein of 38 kDa binds to the cAMP-RE and several proteins of 48-84 kDa bind to the PMA-RE.

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Section: Discussionsupporting

confidence: 88%

Cyclic AMP and phorbol ester-stimulated transcription mediated by similar DNA elements that bind distinct proteins.

Deutsch

Hoeffler

Jameson

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

177

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“…4) is a representative subject. After a lag period of [4][5][6] weeks, her antibodies increased progressively and attained plateau levels around 4 months. The plateau was maintained for about 3 to take care of HCG produced in the event of a pregnancy.…”

Section: Antibodymentioning

confidence: 99%

“…The hormone has a crucial role in establishment and maintenance of pregnancy. HCG is not normally produced by nonpregnant females; the only exceptions are patients with choriocarcinomas (2), hydatidiform mole (3), and patients with cancers that ectopically synthesize the hormone (4,5). Its early appearance and obligatory role in pregnancy make it a suitable target for control of fertility.…”

mentioning

confidence: 99%

Isoimmunization against human chorionic gonadotropin with conjugates of processed beta-subunit of the hormone and tetanus toxoid.

Talwar¹,

Sharma²,

Dubey³

et al. 1976

Proc. Natl. Acad. Sci. U.S.A.

155

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The immunogenicity of the conjugate prepared from "processed" a-subunit of human chorionic gonadotropin (choriogonadotropin, HCG) and tetanus toxoid has been studied in animals and a human subject. The conjugate elicited the formation of high-affinity (Ka = 109-101' M-') anti-HCG and anti-tetanus antibodies. On primary immunization, the antibody response lasted for several months. Repeat injection of the conjugate in the declining phase of antibody titers produced a booster response without a lag period. The antibodies reacted with the ,8-subunit of HCG and the complete HCG molecule but were devoid of significant crossreactivity with human growth hormone, placental lactogen, follicle-stimulating hormone, thyroid-stimulating hormone, and luteinizing hormone at tonic and surge levels. The antibodies were competent for neutralizing the biological activity of HCG in the mouse uterine weight gain assay, the ventral prostate weight gain assay, and the radioligand assay for binding of 1251-labeled HCG to receptors on corpus luteum. HCG (5000 international units) administered to an immunized subject was completely bound by circulating antibodies. Administration of HCG (in contrast to conjugate) was without booster effect on anti-HCG titers.

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“…There are several reports of paraneoplastic gynaecomastia secondary to thoracic (mainly SCLCs, carcinoids and extragonadal germ cell tumours) clinically associated with gynaecomastia in men, menstrual irregularity and virilisation in women, and precocious puberty in children (Braunstein et al 1972, DeLellis & Xia 2003, Yaturu et al 2003, Mehta et al 2008, Dimitriadis et al 2017. Rarely, secretion of bhCG results from clear cell renal tumours (Mohammed et al 2008) or liver carcinomas (Teniola & Ogunleye 1994).…”

Section: Less Common Endocrine Pns Secondary To the Secretion Of Peptmentioning

confidence: 99%

Paraneoplastic endocrine syndromes

Dimitriadis

Angelousi

Weickert

et al. 2017

Endocrine-Related Cancer

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The majority of neoplasms are responsible for symptoms caused by mass effects to surrounding tissues and/or through the development of metastases. However, occasionally neoplasms, with or without endocrine differentiation, acquire the ability to secrete a variety of bioactive substances or induce immune cross-reactivity with the normal tissues that can lead to the development of characteristic clinical syndromes. These syndromes are named endocrine paraneoplastic syndromes when the specific secretory components (hormones, peptides or cytokines) are unrelated to the anticipated tissue or organ of origin. Endocrine paraneoplastic syndromes can complicate the patient's clinical course, response to treatment, impact prognosis and even be confused as metastatic spread. These syndromes can precede, occur concomitantly or present at a later stage of tumour development, and along with the secreted substances constitute the biological 'fingerprint' of the tumour. Their detection can facilitate early diagnosis of the underlying neoplasia, monitor response to treatment and/or detect early recurrences following successful initial management. Although when associated with tumours of low malignant potential they usually do not affect long-term outcome, in cases of highly malignant tumours, endocrine paraneoplastic syndromes are usually associated with poorer survival outcomes. Recent medical advances have not only improved our understanding of paraneoplastic syndrome pathogenesis in general but also enhanced their diagnosis and treatment. Yet, given the rarity of endocrine paraneoplastic syndromes, there is a paucity of prospective clinical trials to guide management. The development of well-designed prospective multicentre trials remains a priority in the field in order to fully characterise these syndromes and provide evidence-based diagnostic and therapeutic protocols.

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In Vivoandin VitroProduction of Human Chorionic Gonadotropin and Alpha-Fetoprotein by a Virilizing Hepatoblastoma

Cited by 62 publications

References 0 publications

Cyclic AMP and phorbol ester-stimulated transcription mediated by similar DNA elements that bind distinct proteins.

Cyclic AMP and phorbol ester-stimulated transcription mediated by similar DNA elements that bind distinct proteins.

Isoimmunization against human chorionic gonadotropin with conjugates of processed beta-subunit of the hormone and tetanus toxoid.

Paraneoplastic endocrine syndromes

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