Hugl1 and Hugl2 in mammary epithelial cells: polarity, proliferation, and differentiation
Loss of epithelial polarity is described as a hallmark of epithelial cancer. To determine the role of Hugl1 and Hugl2 expression in the breast, we investigated their localization in human mammary duct tissue and the effects of expression modulation in normal and cancer cell lines on polarity, prolif...
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| description | Loss of epithelial polarity is described as a hallmark of epithelial cancer. To determine the role of Hugl1 and Hugl2 expression in the breast, we investigated their localization in human mammary duct tissue and the effects of expression modulation in normal and cancer cell lines on polarity, proliferation and differentiation. Expression of Hugl1 and Hugl2 was silenced in both MCF10A cells and Human Mammary Epithelial Cells and cell lines were grown in 2-D on plastic and in 3-D in Matrigel to form acini. Cells in monolayer were compared for proliferative and phenotypic changes while acini were examined for differences in size, ability to form a hollow lumen, nuclear size and shape, and localization of key domain-specific proteins as a measure of polarity. We detected overlapping but distinct localization of Hugl1 and Hugl2 in the human mammary gland, with Hugl1 expressed in both luminal and myoepithelium and Hugl2 largely restricted to myoepithelium. On a plastic surface, loss of Hugl1 or Hugl2 in normal epithelium induced a mesenchymal phenotype, and these cells formed large cellular masses when grown in Matrigel. In addition, loss of Hugl1 or Hugl2 expression in MCF10A cells resulted in increased proliferation on Matrigel, while gain of Hugl1 expression in tumor cells suppressed proliferation. Loss of polarity was also observed with knockdown of either Hugl1 or Hugl2, with cells growing in Matrigel appearing as a multilayered epithelium, with randomly oriented Golgi and multiple enlarged nuclei. Furthermore, Hugl1 knock down resulted in a loss of membrane identity and the development of cellular asymmetries in Human Mammary Epithelial Cells. Overall, these data demonstrate an essential role for both Hugl1 and Hugl2 in the maintenance of breast epithelial polarity and differentiated cell morphology, as well as growth control. |
| doi_str_mv | 10.1371/journal.pone.0047734 |
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To determine the role of Hugl1 and Hugl2 expression in the breast, we investigated their localization in human mammary duct tissue and the effects of expression modulation in normal and cancer cell lines on polarity, proliferation and differentiation. Expression of Hugl1 and Hugl2 was silenced in both MCF10A cells and Human Mammary Epithelial Cells and cell lines were grown in 2-D on plastic and in 3-D in Matrigel to form acini. Cells in monolayer were compared for proliferative and phenotypic changes while acini were examined for differences in size, ability to form a hollow lumen, nuclear size and shape, and localization of key domain-specific proteins as a measure of polarity. We detected overlapping but distinct localization of Hugl1 and Hugl2 in the human mammary gland, with Hugl1 expressed in both luminal and myoepithelium and Hugl2 largely restricted to myoepithelium. On a plastic surface, loss of Hugl1 or Hugl2 in normal epithelium induced a mesenchymal phenotype, and these cells formed large cellular masses when grown in Matrigel. In addition, loss of Hugl1 or Hugl2 expression in MCF10A cells resulted in increased proliferation on Matrigel, while gain of Hugl1 expression in tumor cells suppressed proliferation. Loss of polarity was also observed with knockdown of either Hugl1 or Hugl2, with cells growing in Matrigel appearing as a multilayered epithelium, with randomly oriented Golgi and multiple enlarged nuclei. Furthermore, Hugl1 knock down resulted in a loss of membrane identity and the development of cellular asymmetries in Human Mammary Epithelial Cells. Overall, these data demonstrate an essential role for both Hugl1 and Hugl2 in the maintenance of breast epithelial polarity and differentiated cell morphology, as well as growth control.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0047734</identifier><identifier>PMID: 23110097</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biology ; Biotechnology ; Blotting, Western ; Breast cancer ; Cancer ; Cell cycle ; Cell differentiation ; Cell Differentiation - physiology ; Cell division ; Cell Line, Tumor ; Cell morphology ; Cell Polarity - physiology ; Cell Proliferation ; Cellular biology ; Collagen ; Colorectal cancer ; Cytology ; Cytoskeletal Proteins - metabolism ; Cytoskeletal Proteins - physiology ; Differentiation ; Drosophila ; Drug Combinations ; Epithelial cells ; Epithelial Cells - metabolism ; Epithelium ; Female ; Fluorescent Antibody Technique ; Gene Expression Regulation - physiology ; Gene Knockdown Techniques ; Genetics ; Genotype & phenotype ; Golgi apparatus ; Humans ; Image Processing, Computer-Assisted ; Insects ; Interdisciplinary aspects ; Laminin ; Localization ; Mammary gland ; Mammary glands ; Mammary Glands, Human - cytology ; Medicine ; Melanoma ; Mesenchyme ; Metastasis ; Microscopy, Fluorescence ; Morphogenesis ; Morphology ; Nuclei ; Phosphorylation ; Plastics ; Polarity ; Polarity (Biology) ; Proteins ; Proteoglycans ; Rodents ; Skin cancer ; Tetrazolium Salts ; Thiazoles ; Tumor cell lines ; Tumor cells ; Tumors</subject><ispartof>PloS one, 2012-10, Vol.7 (10), p.e47734-e47734</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>Russ et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Russ et al 2012 Russ et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-83bfde716c14178a2299abdb1438406e9e13a937fc097a9ca087f7dc6d8367393</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479147/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479147/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23110097$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Oshima, Robert</contributor><creatorcontrib>Russ, Atlantis</creatorcontrib><creatorcontrib>Louderbough, Jeanne M V</creatorcontrib><creatorcontrib>Zarnescu, Daniela</creatorcontrib><creatorcontrib>Schroeder, Joyce A</creatorcontrib><title>Hugl1 and Hugl2 in mammary epithelial cells: polarity, proliferation, and differentiation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Loss of epithelial polarity is described as a hallmark of epithelial cancer. To determine the role of Hugl1 and Hugl2 expression in the breast, we investigated their localization in human mammary duct tissue and the effects of expression modulation in normal and cancer cell lines on polarity, proliferation and differentiation. Expression of Hugl1 and Hugl2 was silenced in both MCF10A cells and Human Mammary Epithelial Cells and cell lines were grown in 2-D on plastic and in 3-D in Matrigel to form acini. Cells in monolayer were compared for proliferative and phenotypic changes while acini were examined for differences in size, ability to form a hollow lumen, nuclear size and shape, and localization of key domain-specific proteins as a measure of polarity. We detected overlapping but distinct localization of Hugl1 and Hugl2 in the human mammary gland, with Hugl1 expressed in both luminal and myoepithelium and Hugl2 largely restricted to myoepithelium. On a plastic surface, loss of Hugl1 or Hugl2 in normal epithelium induced a mesenchymal phenotype, and these cells formed large cellular masses when grown in Matrigel. In addition, loss of Hugl1 or Hugl2 expression in MCF10A cells resulted in increased proliferation on Matrigel, while gain of Hugl1 expression in tumor cells suppressed proliferation. Loss of polarity was also observed with knockdown of either Hugl1 or Hugl2, with cells growing in Matrigel appearing as a multilayered epithelium, with randomly oriented Golgi and multiple enlarged nuclei. Furthermore, Hugl1 knock down resulted in a loss of membrane identity and the development of cellular asymmetries in Human Mammary Epithelial Cells. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Russ, Atlantis</au><au>Louderbough, Jeanne M V</au><au>Zarnescu, Daniela</au><au>Schroeder, Joyce A</au><au>Oshima, Robert</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hugl1 and Hugl2 in mammary epithelial cells: polarity, proliferation, and differentiation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-10-23</date><risdate>2012</risdate><volume>7</volume><issue>10</issue><spage>e47734</spage><epage>e47734</epage><pages>e47734-e47734</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Loss of epithelial polarity is described as a hallmark of epithelial cancer. To determine the role of Hugl1 and Hugl2 expression in the breast, we investigated their localization in human mammary duct tissue and the effects of expression modulation in normal and cancer cell lines on polarity, proliferation and differentiation. Expression of Hugl1 and Hugl2 was silenced in both MCF10A cells and Human Mammary Epithelial Cells and cell lines were grown in 2-D on plastic and in 3-D in Matrigel to form acini. Cells in monolayer were compared for proliferative and phenotypic changes while acini were examined for differences in size, ability to form a hollow lumen, nuclear size and shape, and localization of key domain-specific proteins as a measure of polarity. We detected overlapping but distinct localization of Hugl1 and Hugl2 in the human mammary gland, with Hugl1 expressed in both luminal and myoepithelium and Hugl2 largely restricted to myoepithelium. On a plastic surface, loss of Hugl1 or Hugl2 in normal epithelium induced a mesenchymal phenotype, and these cells formed large cellular masses when grown in Matrigel. In addition, loss of Hugl1 or Hugl2 expression in MCF10A cells resulted in increased proliferation on Matrigel, while gain of Hugl1 expression in tumor cells suppressed proliferation. Loss of polarity was also observed with knockdown of either Hugl1 or Hugl2, with cells growing in Matrigel appearing as a multilayered epithelium, with randomly oriented Golgi and multiple enlarged nuclei. Furthermore, Hugl1 knock down resulted in a loss of membrane identity and the development of cellular asymmetries in Human Mammary Epithelial Cells. Overall, these data demonstrate an essential role for both Hugl1 and Hugl2 in the maintenance of breast epithelial polarity and differentiated cell morphology, as well as growth control.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23110097</pmid><doi>10.1371/journal.pone.0047734</doi><tpages>e47734</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biology Biotechnology Blotting, Western Breast cancer Cancer Cell cycle Cell differentiation Cell Differentiation - physiology Cell division Cell Line, Tumor Cell morphology Cell Polarity - physiology Cell Proliferation Cellular biology Collagen Colorectal cancer Cytology Cytoskeletal Proteins - metabolism Cytoskeletal Proteins - physiology Differentiation Drosophila Drug Combinations Epithelial cells Epithelial Cells - metabolism Epithelium Female Fluorescent Antibody Technique Gene Expression Regulation - physiology Gene Knockdown Techniques Genetics Genotype & phenotype Golgi apparatus Humans Image Processing, Computer-Assisted Insects Interdisciplinary aspects Laminin Localization Mammary gland Mammary glands Mammary Glands, Human - cytology Medicine Melanoma Mesenchyme Metastasis Microscopy, Fluorescence Morphogenesis Morphology Nuclei Phosphorylation Plastics Polarity Polarity (Biology) Proteins Proteoglycans Rodents Skin cancer Tetrazolium Salts Thiazoles Tumor cell lines Tumor cells Tumors |
| title | Hugl1 and Hugl2 in mammary epithelial cells: polarity, proliferation, and differentiation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T13%3A25%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hugl1%20and%20Hugl2%20in%20mammary%20epithelial%20cells:%20polarity,%20proliferation,%20and%20differentiation&rft.jtitle=PloS%20one&rft.au=Russ,%20Atlantis&rft.date=2012-10-23&rft.volume=7&rft.issue=10&rft.spage=e47734&rft.epage=e47734&rft.pages=e47734-e47734&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0047734&rft_dat=%3Cgale_plos_%3EA498251259%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1345649953&rft_id=info:pmid/23110097&rft_galeid=A498251259&rft_doaj_id=oai_doaj_org_article_2aa39f6ac9a948bf88617eed6e502b1d&rfr_iscdi=true |