Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2011

01-11-2011 | Preclinical study

CAML promotes prolactin-dependent proliferation of breast cancer cells by facilitating prolactin receptor signaling pathways

Authors: Ji-Hong Lim, Tae-You Kim, Woo-Ho Kim, Jong-Wan Park

Published in: Breast Cancer Research and Treatment | Issue 1/2011

Login to get access

Abstract

Calcium-modulating cyclophilin ligand (CAML) interacts with the intracellular regions of various types of membrane-bound receptors, and is required for signaling pathways that involve these receptors. The authors tested the possibility that CAML interacts with prolactin receptor (PRLR) and participates in the prolactin (PRL)-dependent proliferation of breast cancer cells. Breast cancer cell lines were found to express CAML at higher levels than cell lines originating from leukemia and other cancers. Furthermore, immunohistochemical analyses of breast tissue arrays showed that the CAML levels were higher in cancer tissues than in normal tissues. In breast cancer cells and transfected HEK293 cells, CAML associated with PRLR, and this interaction was augmented during PRL stimulation. CAML-silencing experiments revealed that CAML is required for the functions of PRLR, such as, the activations of Stat5 and Mek1/2, PRL internalization with cyclophilin B, PRLR recycling, and increased Ca2+ mobilization. In addition, CAML was found to play a crucial role in the PRL/PRLR-dependent growth of breast cancer cells. These results suggest a new role for CAML in breast cancer development.
Appendix
Available only for authorised users
Literature
1.
Ben-Jonathan N, Mershon JL, Allen DL, Steinmetz RW (1996) Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects. Endocr Rev 17:639–669PubMed
2.
Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA (1998) Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev 19:225–268PubMedCrossRef
3.
Naylor MJ, Lockefeer JA, Horseman ND, Ormandy CJ (2003) Prolactin regulates mammary epithelial cell proliferation via autocrine/paracrine mechanism. Endocrine 20:111–114PubMedCrossRef
4.
Harris J, Stanford PM, Oakes SR, Ormandy CJ (2004) Prolactin and the prolactin receptor: new targets of an old hormone. Ann Med 36:414–425PubMedCrossRef
5.
Clevenger CV, Furth PA, Hankinson SE, Schuler LA (2003) The role of prolactin in mammary carcinoma. Endocr Rev 24:1–27PubMedCrossRef
6.
Miyoshi K, Shillingford JM, Smith GH, Grimm SL, Wagner KU, Oka T, Rosen JM, Robinson GW, Hennighausen L (2001) Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium. J Cell Biol 155:531–542PubMedCrossRef
7.
Clevenger CV, Gadd SL, Zheng J (2009) New mechanisms for PRLr action in breast cancer. Trends Endocrinol Metab 20:223–229PubMedCrossRef
8.
Das R, Vonderhaar BK (1996) Activation of raf-1, MEK, and MAP kinase in prolactin responsive mammary cells. Breast Cancer Res Treat 40:141–149PubMedCrossRef
9.
Tessier C, Prigent-Tessier A, Ferguson-Gottschall S, Gu Y, Gibori G (2001) PRL antiapoptotic effect in the rat decidua involves the PI3 K/protein kinase B-mediated inhibition of caspase-3 activity. Endocrinology 142:4086–4094PubMedCrossRef
10.
Rycyzyn MA, Clevenger CV (2002) The intranuclear prolactin/cyclophilin B complex as a transcriptional inducer. Proc Natl Acad Sci USA 99:6790–6795PubMedCrossRef
11.
Bram RJ, Crabtree GR (1994) Calcium signalling in T cells stimulated by a cyclophilin B-binding protein. Nature 371:355–358PubMedCrossRef
12.
von Bülow GU, Bram RJ (1997) NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily. Science 278:138–141CrossRef
13.
Holloway MP, Bram RJ (1996) A hydrophobic domain of Ca2 + -modulating cyclophilin ligand modulates calcium influx signaling in T lymphocytes. J Biol Chem 271:8549–8852PubMedCrossRef
14.
Holloway MP, Bram RJ (1998) Co-localization of calcium-modulating cyclophilin ligand with intracellular calcium pools. J Biol Chem 273:16346–16350PubMedCrossRef
15.
Tran DD, Russell HR, Sutor SL, van Deursen J, Bram RJ (2003) CAML is required for efficient EGF receptor recycling. Dev Cell 5:245–256PubMedCrossRef
16.
Guang W, Kim KC, Lillehoj EP (2009) MUC1 mucin interacts with calcium-modulating cyclophilin ligand. Int J Biochem Cell Biol 41:1354–1360PubMedCrossRef
17.
Yuan X, Yao J, Norris D, Tran DD, Bram RJ, Chen G, Luscher B (2008) Calcium-modulating cyclophilin ligand regulates membrane trafficking of postsynaptic GABA(A) receptors. Mol Cell Neurosci 38:277–289PubMedCrossRef
18.
Matsumura I, Kitamura T, Wakao H, Tanaka H, Hashimoto K, Albanese C, Downward J, Pestell RG, Kanakura Y (1999) Transcriptional regulation of the cyclin D1 promoter by STAT5: its involvement in cytokine-dependent growth of hematopoietic cells. EMBO J 18:1367–1377PubMedCrossRef
19.
20.
Wennbo H, Gebre-Medhin M, Gritli-Linde A, Ohlsson C, Isaksson OG, Törnell J (1997) Activation of the prolactin receptor but not the growth hormone receptor is important for induction of mammary tumors in transgenic mice. J Clin Invest 100:2744–2751PubMedCrossRef
21.
Rose-Hellekant TA, Arendt LM, Schroeder MD, Gilchrist K, Sandgren EP, Schuler LA (2003) Prolactin induces ERalpha-positive and ERalpha-negative mammary cancer in transgenic mice. Oncogene 22:4664–4674PubMedCrossRef
22.
Clevenger CV, Chang WP, Ngo W, Pasha TL, Montone KT, Tomaszewski JE (1995) Expression of prolactin and prolactin receptor in human breast carcinoma. Evidence for an autocrine/paracrine loop. Am J Pathol 146:695–705PubMed
23.
Reynolds C, Montone KT, Powell CM, Tomaszewski JE, Clevenger CV (1997) Expression of prolactin and its receptor in human breast carcinoma. Endocrinology 138:5555–5560PubMedCrossRef
24.
Hankinson SE, Willett WC, Michaud DS, Manson JE, Colditz GA, Longcope C, Rosner B, Speizer FE (1999) Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 91:629–634PubMedCrossRef
25.
Gill S, Peston D, Vonderhaar BK, Shousha S (2001) Expression of prolactin receptors in normal, benign, and malignant breast tissue: an immunohistological study. J Clin Pathol 54:956–960PubMedCrossRef
26.
Bhatavdekar JM, Patel DD, Shah NG, Vora HH, Suthar TP, Ghosh N, Chikhlikar PR, Trivedi TI (2000) Prolactin as a local growth promoter in patients with breast cancer: GCRI experience. Eur J Surg Oncol 26:540–547PubMedCrossRef
27.
Alvarez RH, Valero V, Hortobagyi GN (2010) Emerging targeted therapies for breast cancer. J Clin Oncol 28:3366–3379PubMedCrossRef
28.
Di Cosimo S, Baselga J (2008) Targeted therapies in breast cancer: where are we now? Eur J Cancer 44:2781–2790PubMedCrossRef
Metadata
Title
CAML promotes prolactin-dependent proliferation of breast cancer cells by facilitating prolactin receptor signaling pathways
Authors
Ji-Hong Lim
Tae-You Kim
Woo-Ho Kim
Jong-Wan Park
Publication date
01-11-2011
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2011
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-010-1274-4

Other articles of this Issue 1/2011

Breast Cancer Research and Treatment 1/2011 Go to the issue

Brief Report

Distinct expressions of microRNAs that directly target estrogen receptor α in human breast cancer

Epidemiology

Breast cancer risk assessment in women aged 70 and older

Epidemiology

Absenteeism and short-term disability associated with breast cancer

Preclinical study

PH006, a novel and selective Src kinase inhibitor, suppresses human breast cancer growth and metastasis in vitro and in vivo

Preclinical study

Post-lumpectomy intracavitary retention and lymph node targeting of 99mTc-encapsulated liposomes in nude rats with breast cancer xenograft

Epidemiology

Correlates of fear of cancer recurrence in women with ductal carcinoma in situ and early invasive breast cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits