Sebastian Giulianelli

Instituto de Biología de Organismos Marinos (IBIOMAR) - National Scientific and Technical Research Council · Laboratorio de Reproducción y Biología Integrativa de Invertebrados Marinos (LARBIM)

Progesterone receptors (PR) play a pivotal role in many female reproductive tissues such as the uterus, the ovary, and the mammary gland (MG). Moreover, PR play a key role in breast cancer growth and progression. This has led to the development and study of different progestins and antiprogestins, many of which are currently being tested in clinica...

Anti-Müllerian hormone (AMH) is secreted by Sertoli cells of the testes from early fetal life until puberty, when it is downregulated by androgens. In conditions like complete androgen insensitivity syndrome (CAIS), AMH downregulation does not occur and AMH increases at puberty, due in part to follicle-stimulating hormone (FSH) effect. However, oth...

The superposition of male sexual characteristics in female marine gastropods (imposex) represents one of the clearest ecological examples of organotin-mediated endocrine disruption. Recent evidences suggest that signaling pathways mediated by members of the nuclear receptor superfamily, RXR and PPARγ, are involved in the development of this pseudoh...

Progression to hormone‐independent growth leading to endocrine therapy resistance occurs in a high proportion of patients with estrogen receptor alpha (ERα) and progesterone receptors (PR) positive breast cancer. We and others have previously shown that estrogen‐ and progestin‐induced tumor growth requires ERα and PR interaction at their target gen...

Progesterone receptors (PR) are prognostic and predictive biomarkers in hormone-dependent cancers. Two main PR isoforms have been described, PRB and PRA, that differ only in that PRB has 164 extra N-terminal amino acids. It has been reported that several antibodies empirically exclusively recognize PRA in formalin-fixed paraffin-embedded tissues (F...

Environmental temperature is increasing while natural populations are forced to develop their life cycle under new conditions, resulting in the expression of new phenotypic traits. Still, the links between these new environmental conditions and the subsequent phenotypic expressions are not fully explored. Here, we conducted manipulative experiments...

Species undergoing postreproductive death experience great changes in their reproductive organs, which are driven by numerous physiological processes. To assess whether apoptotic processes are involved in the dynamics of the reproductive organs of Pleurobranchaea maculata, the gonadal structure of this semelparous side-gilled sea slug was studied u...

Luminal breast cancer (BrCa) has a favorable prognosis compared to other tumor subtypes. However, with time tumors may evolve and lead to disease progression. Thus, there is a great interest in unraveling the mechanisms that drive tumor metastasis and endocrine resistance. In this review we focused in one of the many pathways that have been involve...

Climate change has consequences over marine organisms and their behavior. Echinoderms have been found to be negatively affected on righting time, survival, feeding rate or growth by high temperatures, low salinity or their interaction. We analyzed the effects of temperature and salinity fluctuation under a climate change scenario on feeding rate, r...

Progesterone receptors (PRs) ligands are being tested in luminal breast cancer. There are mainly two PR isoforms, PRA and PRB, and their ratio (PRA/PRB) may be predictive of antiprogestin response. Our aim was to investigate: the impact of the PR isoform ratio on metastatic behaviour, the PR isoform ratio in paired primary tumours and lymph node me...

Environments with strong gradients in physical conditions, such as rocky intertidal, induce animal morphological strategies to face them. The gastropod Trophon geversianus inhabit within the intertidal and subtidal habitats of Patagonian rocky shores. Although there is a wide knowledge of the phenotypic differences of this species regarding habitat...

Background The use of progesterone receptor (PR) ligands for adjuvant breast cancer treatment remains controversial. We propose that antiprogestins inhibit the breast tumor growth with high isoform A (PRA)/isoform B (PRB) ratio while progestins may inhibit those with opposite ratios. Methods We used metastatic models with different PR isoform rati...

Seventy percent of breast cancer patients are susceptible to endocrine therapy. Interactions between estrogen receptor alpha (ERα) and progesterone receptors (PR) at gene promoters have been recently demonstrated after hormone priming. The aim of this study was to determine whether growth factor signaling, namely that triggered by FGF2, could activ...

The marine gastropod Buccinanops globulosus is known to have high imposex incidence in areas moderately polluted by tributyltin (TBT). Acute toxicity was previously studied in adults but no information is known about embryonic intracapsular development. To estimate the potential effects of organotin pollution on the progeny of B. globulosus, acute...

In previous studies using several experimental models expressing different progesterone receptor (PR) isoform ratios, we have shown that only those with high levels of isoform A (PRA) are inhibited by antiprogestins whereas those with high levels of isoform B (PRB) are resistant to antiprogestin therapy. Moreover, results obtained using tissue cult...

Buccinanops globulosus and Trophon geversianus are high and low sensitive to TBT. LD50 was 5.41 and 6.21 μgTBT.g-1bw for B. globulosus and T. geversianus respectively, denoting high resistance to TBT acute exposure. These results can be used for future imposex induction experiments.

Buccinanops globulosus and Trophon geversianus are high and low sensitive to TBT. LD50 was 5.41 and 6.21 μgTBT.g-1bw for B. globulosus and T. geversianus respectively, denoting high resistance to TBT acute exposure. These results can be used for future imposex induction experiments.

There is emerging interest in understanding the role of progesterone receptors (PRs) in breast cancer. The aim of this study was to investigate the proliferative effect of progestins and antiprogestins depending on the relative expression of the A (PRA) and B (PRB) isoforms of PR. In mifepristone (MFP)-resistant murine carcinomas antiprogestin resp...

AMH is expressed at high levels in prepubertal Sertoli cells of the testis. FSH increases, whereas androgens inhibit, testicular AMH production. In patients with Androgen Insensitivity Syndrome or with Peutz-Jeghers Syndrome, AMH testicular production is increased, concomitantly with estradiol. The AMH promoter contains an estrogen response element...

Las células de Sertoli del testículo prepuberal producen altos niveles de AMH. La FSH estimula y los andrógenos inhiben dicha producción durante la pubertad. En ciertas patologías, como la insensibilidad a los andrógenos, aumentan los niveles de FSH, AMH y E2. El promotor humano de la AMH (5’hAMH) posee un hemisitio de respuesta a estrógenos (½-ERE...

Estrogen and progesterone receptors (ER and PR respectively) are prognostic markers and dictate therapeutic decisions in breast cancer patients. Although most of the evidence suggests that estrogens are the major etiological factors in breast cancer, there is experimental and epidemiological data that also points to the involvement of PR in mammary...

An increasing body of evidence indicates that progesterone receptors (PR) represent an important regulator of breast cancer growth. In the last years our group has been investigating the mechanisms by which antiprogestins induce the regression of murine mammary carcinomas, showing that only those expressing levels of PR isoform A (PRA) higher than...

Hormone receptors represent the earliest biomarkers used in breast cancer not only as prognosis markers but, in addition, to decide treatment. However, mostly estrogen receptors have been used as therapeutic targets. There is compelling evidence indicating that progesterone receptors (PRs) play a hierarchical role in breast cancer growth and that t...

We have previously demonstrated in a mouse model of breast cancer that mammary carcinomas which are responsive to the antiprogestin mifepristone (MFP) express higher levels of isoform A of progesterone receptor (PRA) than isoform B (PRB). PRB is predominant in tumors with constitutive or acquired resistance to MFP, indicating that the PR isoform ra...

In C4-HD murine mammary carcinomas and in human breast cancer T47D cells, we showed that medroxyprogesterone acetate (MPA) induces a nuclear physical association between estrogen receptor alpha (ERa) and progesterone receptors (PR). The blockade of ERa inhibits cell proliferation mediated by progestins. We hypothesized that this nuclear association...

En carcinomas mamarios murinos (C4-HD) y en células de cáncer de mama humano (T47D) observamos que el progestágeno sintético, acetato de medroxiprogesterona (MPA), induce la activación del receptor de estrógenos alfa (REa) y su asociación nuclear con el receptor de progesterona (RP). En este trabajo postulamos que dicha interacción a nivel genómico...

Synthetic progesterone used in contraception drugs (progestins) can promote breast cancer growth, but the mechanisms involved are unknown. Moreover, it remains unclear whether cytoplasmic interactions between the progesterone receptor (PR) and estrogen receptor alpha (ERα) are required for PR activation. In this study, we used a murine progestin-de...

The mechanisms by which progestins participate in breast cancer growth are not completely elucidated. Although most of the evidence suggests estrogens as the major etiological factor in breast cancer, there is experimental and epidemiological data that also points to the involvement of the progesterone receptors (PR) in mammary gland carcinogenesis...

It is well known that estrogens are key players regulating breast cancer growth. In addition, there is compelling evidence pointing out that progestins induce proliferative effects in normal and in neoplastic mammary glands. Using a murine breast cancer model, first developed in the National Academy of Medicine in Buenos Aires, and then moved to th...

Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and...

The nuclear receptor coactivator AIB1 (SRC-3) is intimately associated with hormone action in estrogen receptor (ER)-positive breast cancer, and its overexpression has been associated with early resistance to endocrine therapy. In two models of ER+, progesterone receptor (PR)+ breast cancer, human T47D cells growing in vitro and C4-HD and C4-HI mou...

Two-thirds of diagnosed breasts cancers express either estrogen receptors (ER), progesterone receptors (PR) or both. Unlike most experimental breast cancer models, in the medroxyprogesterone acetate (MPA) model, MPA induces mammary carcinomas that express high levels of ER and PR. In this model we developed a tumor variant that depends on MPA to gr...

In this article, we demonstrate the expression of functional progesterone binding sites at the cell membrane in murine mammary carcinomas that are stimulated by progestins and inhibited by antiprogestins. Using confocal immunofluorescence, ligand binding and cell compartment-specific western blots, we were able to identify the presence of the class...

Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and...

We have previously demonstrated a crosstalk between fibroblast growth factor 2 (FGF2) and progestins inducing experimental breast cancer growth. The aim of the present study was to compare the effects of FGF2 and of medroxyprogesterone acetate (MPA) on the mouse mammary glands and to investigate whether the antiprogestin RU486 was able to reverse t...

Over the past several years, we have been interested in understanding the mechanisms by which mammary carcinomas acquire hormone independence. We demonstrated that carcinoma associated fibroblasts participate in the ligand-independent activation of progesterone receptors inducing tumor growth. In this study, we used DNA microarrays to compare the g...

Most breast carcinomas that are estrogen receptor (ER) and progesterone receptor (PR) positive respond initially to an endocrine therapy, but over time, they develop resistance (acquired hormone resistance). Others, however, fail to respond from the beginning (constitutive resistance). Overcoming hormone resistance is one of the major desirable aim...

The expression of estrogen receptor alpha (ERα) and progesterone receptor (PR) in breast cancer is used as a prognostic factor and identifies a group of tumors which may respond to an endocrine therapy aimed to block estrogen synthesis or ER activation. There is however, compelling evidence that indicates that PR is also involved in breast cancer g...

To evaluate the extent to which each estrogen receptor (ER) subtype contributes to the stimulation or to the inhibition of mammary tumor growth, we evaluated the effects of specific agonists in MC4-L2 cells, which are stimulated by 17β-estradiol (E(2)), and in mammary carcinomas of the MPA mouse breast cancer model, which are inhibited by E(2). Bot...

Breast cancer is the most frequent cancer in women. However, in vivo hormone receptor positive and metastatic models are scarce. The aim of the present manuscript was to assess if the novel steroid receptor positive human cell lines IBH-4, IBH-6, and IBH-7 developed in our laboratory from primary infiltrant ductal carcinomas are good models to stud...

More than 60% of all breast neoplasias are ductal carcinomas expressing estrogen (ER) and progesterone receptors (PR). By contrast, most of the spontaneous, chemically or mouse mammary tumor virus induced tumors, as well as tumors arising in genetically modified mice do not express hormone receptors. We developed a model of breast cancer in which t...

The mechanisms by which mammary carcinomas acquire hormone independence are still unknown. To study the role of cancer-associated fibroblasts (CAF) in the acquisition of hormone-independence we used a hormone-dependent (HD) mouse mammary tumor and its hormone-independent (HI) variant, which grows in vivo without hormone supply. HI tumors express hi...

It has been proposed that progesterone (P4) induces the suppression of immune responses, particularly during pregnancy. However, knowledge about the mechanisms involved has remained largely elusive. We demonstrate herein that peripheral blood NK (PBNK) cells express both classical progesterone receptor (PR) isoforms and are specifically affected by...

The mechanisms by which hormone dependent (HD) tumors start growing without hormone supply has been a topic of study in our laboratory. We have developed an experimental model of breast cancer in BALB/c female mice in which metastatic ductal mammary carcinomas transit through different stages of hormone dependence. HD tumors (C4-HD) need the exogen...

The expression of estrogen receptor alpha (ERa) in breast cancer identifies a group of tumors which may respond to an endocrine therapy. Most of these tumors are also progesterone receptor (PR) positive and this has been used as a marker of estrogen action. It has also been postulated that cytosolic PR isoform B (PRB) interacts with ERa and activat...

We have developed an experimental model of mouse mammary carcinomas expressing high levels of hormone receptors which transit through different stages of hormone dependence. In this study we have demonstrated that carcinoma associated fibroblasts (CAF) from hormone independent tumors (HI) express higher levels of FGF-2 than those of hormone-depende...

We have developed an experimental model of breast cancer in BALB/c female mice in which metastatic ductal mammary carcinomas transit through different stages of hormone dependence. HD tumors need the exogenous administration of progestins to grow while hormone-independent (HI) carcinomas grow in vivo without exogenous progestin supply, although the...

Prostaglandin F2alpha (PGF2alpha) induces cyclin D1 expression and DNA synthesis in Swiss 3T3 cells. In order to assess which signaling mechanisms are implicated in these processes, we have used both a pharmacological approach and interfering mutants. We demonstrate that PGF2alpha induces extracellular-signal-regulated kinase (ERK1-2) and p38MAPK a...

Previous data from our laboratory suggested that progesterone receptors (PRs) are involved in progestin-independent growth of mammary carcinomas. To investigate this possibility further, we studied the effects of PR antisense oligodeoxynucleotides (asPR) on in vivo tumor growth. BALB/c mice with subcutaneous 25 mm2 mammary carcinomas expressing est...

Leukaemia inhibitory factor (LIF) or Oncostatin M (OSM), both mitogens for Swiss mouse 3T3 cells, triggers initiation of DNA synthesis without the requirement for mevalonic acid. Thus, Lovastatin (LOV), an inhibitor of the hydroxy methylglutaryl CoA (HMGCoA) reductase, does not block LIF or OSM induced DNA replication and cell multiplication. In co...