Nerve growth factor and bromocriptine: a sequential therapy for human bromocriptine-resistant prolactinomas

Missale, Cristina; Losa, Marco; Boroni, F.; Giovanelli, Massimo; Balsari, Andrea; Spano, PierFranco

doi:10.1038/bjc.1995.520

Cited by 23 publications

(14 citation statements)

References 9 publications

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“…We found that NGFR (subtype p75 NGFR ) was expressed at a lower level in patients with prolactinomas classified as resistant to DA, which is in accordance with the findings of other authors [27]. NGFB and NGFR have also been involved with DA responsiveness in prolactinomas [25].…”

Section: Discussionsupporting

confidence: 80%

“…Missale et al [27] also demonstrated that after treatment with NGFB for 4 days, prolactinoma cells resistant to DA in culture reduced their proliferation rate and ability to develop colonies in agar, lost their tumorigenic activity in nude mice and re-expressed DRD 2 . These effects remained even after NGFB withdrawal.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a negative correlation between ERB and NGFB expression and a positive correlation between ERB and PTTG were found. This could suggest that ERB could play a role in the more aggressive behavior that some authors describe in resistant prolactinomas [27]. …”

Section: Discussionmentioning

confidence: 99%

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Genes Differentially Expressed in Prolactinomas Responsive and Resistant to Dopamine Agonists

Passos¹,

Fortes

Giannella-Neto

et al. 2008

Neuroendocrinology

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Background/Aims: Prolactin (PRL) secretion and its gene expression are inhibited by dopamine. Prolactinomas are the most common secreting pituitary adenomas, and dopamine agonists (DA) are the first choice for their treatment. However, a subset of patients is resistant to DA. As the mechanisms involved in DA resistance are not fully understood, the aim of this study was to obtain new insights regarding the molecular differences between the prolactinomas that are responsive to DA and those that are resistant. Methods: Tumor tissue samples were collected from 17 patients who harbored prolactinomas, which were classified as responsive or resistant according to their clinical and laboratorial reaction to DA. The expression of 6 genes was evaluated by real-time polymerase chain reaction: dopamine receptor type 2 (DRD₂), nerve growth factor-β (NGFB) and its receptor (NGFR), estrogen receptor-α (ERA), estrogen receptor-β (ERB) and the pituitary tumor transforming gene (PTTG). Results: Median DRD₂ and NGFR expression in responsive patients was significantly higher than in resistant ones (p = 0.029 and p = 0.020, respectively). Moreover, the expressions of DRD₂ and NGFR were positively correlated with PRL decrease during treatment (r = 0.66, p = 0.005 and r = 0.57, p = 0.044, respectively). Furthermore, ERB expression was positively correlated to PTTG expression (r = 0.68, p = 0.032) and negatively correlated to NGFB expression (r = –0.75, p = 0.02). Conclusions: DRD₂ and NGFR expressions are related to the responsiveness of prolactinoma to DA. However, PTTG, ERB and ERA expressions are not. Also ERB, ERA and PTTG expressions did not present a clear correlation to tumor aggressiveness. Furthermore, the response of prolactinomas to DA should be viewed as a spectrum ranging from the most responsive to the most resistant ones.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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Genes Differentially Expressed in Prolactinomas Responsive and Resistant to Dopamine Agonists

Passos¹,

Fortes

Giannella-Neto

et al. 2008

Neuroendocrinology

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“…This issue seems of critical relevance as it is now emerging that NGF is an antiproliferative and differentiation factor for various tumors of neuroendocrine origin (15-21). In particular, NGF has been consistently reported to induce differentiation of the pituitary tumor cell line GH 3 (15) and the insulinoma cell line RINm5F (16,17) and to suppress cell growth and tumorigenicity of human prolactin-secreting adenomas (18,19). In addition, we found that an autocrine loop mediated by NGF is operative in both normal pituitary lactotroph cells (20) and slowly proliferating, nontumorigenic prolactinomas but not in tumorigenic prolactinoma cells (18,21).…”

mentioning

confidence: 54%

Nerve growth factor abrogates the tumorigenicity of human small cell lung cancer cell lines

Missale

Codignola

Sigala

et al. 1998

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

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Nerve growth factor (NGF) has antiproliferative and differentiating effects on adenomas of neuroendocrine origin. Cell lines derived from small-cell lung carcinoma (SCLC), a very aggressive neuroendocrine tumor, express NGF receptors. The role of NGF in the control of proliferation and progression of this carcinoma, however, has never been investigated. Chronic exposure of NCI-N-592 and GLC8 SCLC cell lines to NGF remarkably inhibited their proliferation rate both in vitro and in vivo, prevented their anchorage-independent clonal growth in soft agar, impaired their invasive capacity in vitro, and abolished their tumorigenic potential in nude mice. The proliferative response of SCLC cell lines to nicotine was also remarkably impaired by in vitro NGF treatment. Furthermore, NGF treatment activates in SCLC cell lines the expression and secretion of NGF. NGF thus reverts SCLC cell lines to a noninvasive, nontumorigenic phenotype that does not respond to nicotine and produces NGF.Small-cell lung cancer (SCLC) is a very aggressive human tumor representing about 25% of all lung cancers (1). Although our understanding of the biology of SCLC is expanding rapidly, there have been no recent major advances in the treatment of this tumor, and overall survival has not changed significantly since the late 1970s (1). SCLC has some phenotypical properties of a neuroendocrine tumor such as expression of L-dopa decarboxylase (1, 2), bombesin͞gastrin-releasing peptide (1, 3), neuron-specific enolase (1), and voltage-operated calcium channels of neuronal type (4-6). Proliferation of SCLC is controlled by autocrine loops sustained by the secretion of different neurohormones and growth factors such as bombesin, insulin-like growth factor I, bradykinin, neurotensin, cholecystokinin, and vasopressin (1). A mitogenic loop mediated by serotonin (5-HT) and facilitated by neuronal-type nicotinic receptors through stimulation of 5-HT release (7, 8) has been recently shown to be operative in SCLC cell lines (9, 10).Despite the observation that SCLC cell lines express (11) the tyrosine kinase trkA receptor for NGF (12)(13)(14), the role of this neurotrophin in the control of proliferation, invasiveness, and tumorigenic potential of this tumor has never been investigated. This issue seems of critical relevance as it is now emerging that NGF is an antiproliferative and differentiation factor for various tumors of neuroendocrine origin (15-21). In particular, NGF has been consistently reported to induce differentiation of the pituitary tumor cell line GH 3 (15) and the insulinoma cell line RINm5F (16,17) and to suppress cell growth and tumorigenicity of human prolactin-secreting adenomas (18,19). In addition, we found that an autocrine loop mediated by NGF is operative in both normal pituitary lactotroph cells (20) and slowly proliferating, nontumorigenic prolactinomas but not in tumorigenic prolactinoma cells (18,21). The impact of this mechanism is such that the breakdown of the NGF-mediated autocrine loop in nontumorigenic prolactinoma...

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“…These results were reproduced in nude mice trans planted with nonresponder prolactinomas lacking Dt re ceptors [28], After the formation of measurable tumors, animals were treated with intravenous NGF or saline once a day for 5 consecutive days and then examined for tumor growth for 40 days. NGF treatment remarkably inhibited tumor growth so that 40 days after the last NGF administration the tumor size was about 10-fold smaller when compared with saline-treated controls.…”

Section: Ngf and Pituitary Tum Orsmentioning

confidence: 99%

Nerve Growth Factor Suppresses the Tumoral Phenotype of Human Prolactinomas

et al. 1997

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We summarize here our data showing that various phenotypical characteristics distinguish prolactinoma cell lines obtained from responder and nonresponder patients, as defined by their responses to bromocriptine administration. Nonresponder cell lines have a higher degree of malignancy than responder cells and do not express D₂ receptors for dopamine. Both cell lines express NGF receptors. Exposure of the most malignant nonresponder cell lines to NGF, both in vitro and when transplanted in vivo in nude mice, results in their differentiation into the responder phenotype reexpressing D₂ receptors. Sequential administration of NGF and bromocriptine thus may be a promising therapy for patients refractory to bromocriptine.

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Nerve growth factor and bromocriptine: a sequential therapy for human bromocriptine-resistant prolactinomas

Cited by 23 publications

References 9 publications

Genes Differentially Expressed in Prolactinomas Responsive and Resistant to Dopamine Agonists

Genes Differentially Expressed in Prolactinomas Responsive and Resistant to Dopamine Agonists

Nerve growth factor abrogates the tumorigenicity of human small cell lung cancer cell lines

Nerve Growth Factor Suppresses the Tumoral Phenotype of Human Prolactinomas

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