Sustained trophism of the mammary gland is sufficient to accelerate and synchronize development of ErbB2/Neu-induced tumors.

2.50
Hdl Handle:
http://hdl.handle.net/10146/68618
Title:
Sustained trophism of the mammary gland is sufficient to accelerate and synchronize development of ErbB2/Neu-induced tumors.
Authors:
Landis, M. D.; Seachrist, D. D.; Abdul-Karim, F. W.; Keri, R. A.
Abstract:
Epidemiological studies indicate that parity enhances HER2/ErbB2/Neu-induced breast tumorigenesis. Furthermore, recent studies using multiparous, ErbB2/Neu-overexpressing mouse mammary tumor virus (MMTV-Neu) mice have shown that parity induces a population of cells that are targeted for ErbB2/Neu-induced transformation. Although parity accelerates mammary tumorigenesis, the pattern of tumor development in multiparous MMTV-Neu mice remains stochastic, suggesting that additional events are required for ErbB2/Neu to cause mammary tumors. Whether such events are genetic in nature or reflective of the dynamic hormonal control of the gland that occurs with pregnancy remains unclear. We postulated that young age at pregnancy initiation or chronic trophic maintenance of mammary epithelial cells might provide a cellular environment that significantly increases susceptibility to ErbB2/Neu-induced tumorigenesis. MMTV-Neu mice that were maintained pregnant or lactating beginning at 3 weeks of age demonstrated accelerated tumorigenesis, but this process was still stochastic, indicating that early pregnancy does not provide the requisite events of tumorigenesis. However, bitransgenic mice that were generated by breeding MMTV-Neu mice with a luteinizing hormone-overexpressing mouse model of ovarian hyperstimulation developed multifocal mammary tumors in an accelerated, synchronous manner compared to virgin MMTV-Neu animals. This synchrony of tumor development in the bitransgenic mice suggests that trophic maintenance of the mammary gland provides the additional events required for tumor formation and maintains the population of cells that are targeted by ErbB2/Neu for transformation. Both the synchrony of tumor appearance and the ability to characterize a window of commitment by ovariectomy/palpation studies permitted microarray analysis to evaluate changes in gene expression over a defined timeline that spans the progression from normal to preneoplastic mammary tissue. These approaches led to identification of several candidate genes whose expression changes in the mammary gland with commitment to ErbB2/Neu-induced tumorigenesis, suggesting that they may either be regulated by ErbB2/Neu and/or contribute to tumor formation.
Citation:
Oncogene 2006, 25 (23):3325-3334
Journal:
Oncogene
Issue Date:
1-Jun-2006
URI:
http://hdl.handle.net/10146/68618
DOI:
10.1038/sj.onc.1209365
PubMed ID:
16434967
Additional Links:
http://www.nature.com/onc/journal/v25/n23/abs/1209365a.html; http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16434967
Type:
Article
Language:
en
Description:
KEYWORDS - CLASSIFICATION: analysis;Animals;Cell Transformation,Neoplastic;Female;genetics;lifestyle modulation of cancer & cancer biomarkers;metabolism;Male;Mammary Glands,Animal;Mammary Neoplasms,Experimental;mechanisms of carcinogenesis;Mice;Mice,Transgenic;pathology;physiology;Pregnancy;Pregnancy Complications,Neoplastic;Receptor,erbB-2;Research.
ISSN:
0950-9232
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorLandis, M. D.-
dc.contributor.authorSeachrist, D. D.-
dc.contributor.authorAbdul-Karim, F. W.-
dc.contributor.authorKeri, R. A.-
dc.date.accessioned2009-05-20T10:30:35Z-
dc.date.available2009-05-20T10:30:35Z-
dc.date.issued2006-06-01-
dc.identifier.citationOncogene 2006, 25 (23):3325-3334en
dc.identifier.issn0950-9232-
dc.identifier.pmid16434967-
dc.identifier.doi10.1038/sj.onc.1209365-
dc.identifier.urihttp://hdl.handle.net/10146/68618-
dc.descriptionKEYWORDS - CLASSIFICATION: analysis;Animals;Cell Transformation,Neoplastic;Female;genetics;lifestyle modulation of cancer & cancer biomarkers;metabolism;Male;Mammary Glands,Animal;Mammary Neoplasms,Experimental;mechanisms of carcinogenesis;Mice;Mice,Transgenic;pathology;physiology;Pregnancy;Pregnancy Complications,Neoplastic;Receptor,erbB-2;Research.en
dc.description.abstractEpidemiological studies indicate that parity enhances HER2/ErbB2/Neu-induced breast tumorigenesis. Furthermore, recent studies using multiparous, ErbB2/Neu-overexpressing mouse mammary tumor virus (MMTV-Neu) mice have shown that parity induces a population of cells that are targeted for ErbB2/Neu-induced transformation. Although parity accelerates mammary tumorigenesis, the pattern of tumor development in multiparous MMTV-Neu mice remains stochastic, suggesting that additional events are required for ErbB2/Neu to cause mammary tumors. Whether such events are genetic in nature or reflective of the dynamic hormonal control of the gland that occurs with pregnancy remains unclear. We postulated that young age at pregnancy initiation or chronic trophic maintenance of mammary epithelial cells might provide a cellular environment that significantly increases susceptibility to ErbB2/Neu-induced tumorigenesis. MMTV-Neu mice that were maintained pregnant or lactating beginning at 3 weeks of age demonstrated accelerated tumorigenesis, but this process was still stochastic, indicating that early pregnancy does not provide the requisite events of tumorigenesis. However, bitransgenic mice that were generated by breeding MMTV-Neu mice with a luteinizing hormone-overexpressing mouse model of ovarian hyperstimulation developed multifocal mammary tumors in an accelerated, synchronous manner compared to virgin MMTV-Neu animals. This synchrony of tumor development in the bitransgenic mice suggests that trophic maintenance of the mammary gland provides the additional events required for tumor formation and maintains the population of cells that are targeted by ErbB2/Neu for transformation. Both the synchrony of tumor appearance and the ability to characterize a window of commitment by ovariectomy/palpation studies permitted microarray analysis to evaluate changes in gene expression over a defined timeline that spans the progression from normal to preneoplastic mammary tissue. These approaches led to identification of several candidate genes whose expression changes in the mammary gland with commitment to ErbB2/Neu-induced tumorigenesis, suggesting that they may either be regulated by ErbB2/Neu and/or contribute to tumor formation.en
dc.language.isoenen
dc.relation.urlhttp://www.nature.com/onc/journal/v25/n23/abs/1209365a.htmlen
dc.relation.urlhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16434967en
dc.subjectGene expression profilingen
dc.subjectErbB2/Neu/HER2en
dc.subjectTransgenic miceen
dc.subjectParityen
dc.subjectBreast canceren
dc.subjectMammary glanden
dc.subject.meshAnimals-
dc.subject.meshCell Transformation, Neoplastic-
dc.subject.meshFemale-
dc.subject.meshMale-
dc.subject.meshMammary Glands, Animal-
dc.subject.meshMammary Neoplasms, Experimental-
dc.subject.meshMice-
dc.subject.meshMice, Transgenic-
dc.subject.meshPregnancy-
dc.subject.meshPregnancy Complications, Neoplastic-
dc.subject.meshReceptor, erbB-2-
dc.titleSustained trophism of the mammary gland is sufficient to accelerate and synchronize development of ErbB2/Neu-induced tumors.en
dc.typeArticleen
dc.identifier.journalOncogeneen

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