Role of Prolactin Receptors in Lymphangioleiomyomatosis

Alkharusi, Amira; Lesma, Elena; Ancona, Silvia; Chiaramonte, Eloisa; Nyström, Thomas; Gorio, Alfredo; Norstedt, Gunnar

doi:10.1371/journal.pone.0146653

Cited by 9 publications

(9 citation statements)

References 36 publications

(34 reference statements)

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“…Finally, it is possible that GBM represents a state of either increased Prl production or increased Prl sensitivity. In support of the latter, loss of TSC2 (a well-known suppressor of mTOR) function leads to increased Prl sensitivity of lymphangioleiomyomatosis (LAM) cells, a sarcoma–like cell type [ 36 , 37 ]. The mTOR system is an important signal integrator and regulator of protein synthesis and seems to be over-active in GBM [ 17 , 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

Stimulation of prolactin receptor induces STAT-5 phosphorylation and cellular invasion in glioblastoma multiforme

Alkharusi

Landázuri

et al. 2016

Oncotarget

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Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in humans and is characterized with poor outcome. In this study, we investigated components of prolactin (Prl) system in cell models of GBM and in histological tissue sections obtained from GBM patients. Expression of Prolactin receptor (PrlR) was detected at high levels in U251-MG, at low levels in U87-MG and barely detectable in U373 cell lines and in 66% of brain tumor tissues from 32 GBM patients by immunohistochemical technique. In addition, stimulation of U251-MG and U87-MG cells but not U373 with Prl resulted in increased STAT5 phosphorylation and only in U251-MG cells with increased cellular invasion. Furthermore, STAT5 phosphorylation and cellular invasion induced in Prl stimulated cells were significantly reduced by using a Prl receptor antagonist that consists of Prl with four amino acid replacements. We conclude that Prl receptor is expressed at different levels in the majority of GBM tumors and that blocking of PrlR in U251-MG cells significantly reduce cellular invasion.

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Section: Discussionmentioning

confidence: 99%

Stimulation of prolactin receptor induces STAT-5 phosphorylation and cellular invasion in glioblastoma multiforme

Alkharusi

Landázuri

et al. 2016

Oncotarget

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“…Activation of the PRLR by PRL leads to activation of the JAK/STAT pathway [39,42]. Several publications suggest that activation of the PRL/PRLR signaling pathways is linked to cancer via activation of PI3K, AKT, and MAPK pathways, which are important in tumorigenesis [43][44][45]. These pathways are also known to be activated by HCMV infection.…”

Section: Introductionmentioning

confidence: 99%

Human Cytomegalovirus Infection Induces High Expression of Prolactin and Prolactin Receptors in Ovarian Cancer

Rahbar

Alkharusi

Costa

et al. 2020

Biology

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One of the potential biomarkers for ovarian cancer patients is high serum level of prolactin (PRL), which is a growth factor that may promote tumor cell growth. The prolactin receptor (PRLR) and human cytomegalovirus (HCMV) proteins are frequently detected in ovarian tumor tissue specimens, but the potential impact of HCMV infection on the PRL system have so far not been investigated. In this study, HCMV’s effects on PRL and PRLR expression were assessed in infected ovarian cancer cells (SKOV3) by PCR and Western blot techniques. The levels of both PRL and PRLR transcripts as well as the corresponding proteins were highly increased in HCMV-infected SKOV3 cells. Tissue specimens obtained from 10 patients with ovarian cancer demonstrated high expression of PRLR, HCMV-IE, and pp65 proteins. Extensive expression of PRLR was detected in all examined ovarian tumor tissue specimens except for one from a patient who had focal expression of PRLR and this patient was HCMV-negative in her tumor. In conclusion, PRL and PRLR were induced to high levels in HCMV-infected ovarian cancer cells and PRLR expression was extensively detected in HCMV-infected ovarian tissue specimens. Highly induced PRL and PRLR by HCMV infection may be of relevance for the oncomodulatory role of this virus in ovarian cancer.

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“…The relationship between LAM and PRL is the third point of consideration. Studies have found that LAM cells also contribute to the increased expression of PRL receptors [ 10 ]. Hence, patients with LAM are more susceptible to mTOR activation by PRLs.…”

Section: Discussionmentioning

confidence: 99%

Lymphangioleiomyomatosis associated with prolactinoma: A case report and literature review

Murakami

Tobino

2021

Respiratory Medicine Case Reports

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The thirty-five-year-old woman had been experiencing dyspnea on exertion since her second child's birth five years before presenting to hospital A, where she was diagnosed with lymphangioleiomyomatosis (LAM) based on video-assisted thoracoscopic surgery lung biopsy and referred to our hospital. She was treated with sirolimus for one year. Although her subjective symptom of dyspnea improved, she found that her amenorrhea had persisted for six years. A blood test revealed high prolactin (PRL) levels of 98 ng/mL and head magnetic resonance imaging revealed a pituitary adenoma, which was complicated by a prolactinoma. We continued with follow-up observation without any pharmacotherapy for the prolactinoma. However, she was administered oral cabergoline (0.25 mg per week) when her PRL levels were elevated to 250 ng/mL 38 months after therapeutic intervention with sirolimus. For the next 14 months, her respiratory function and PRL concentration both demonstrated improvement and her condition did not worsen any further. It has been reported that prolactin may exacerbate LAM. Our case suggests that a clinical reduction in PRL levels may also improve LAM.

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Role of Prolactin Receptors in Lymphangioleiomyomatosis

Cited by 9 publications

References 36 publications

Stimulation of prolactin receptor induces STAT-5 phosphorylation and cellular invasion in glioblastoma multiforme

Stimulation of prolactin receptor induces STAT-5 phosphorylation and cellular invasion in glioblastoma multiforme

Human Cytomegalovirus Infection Induces High Expression of Prolactin and Prolactin Receptors in Ovarian Cancer

Lymphangioleiomyomatosis associated with prolactinoma: A case report and literature review

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