LIV-1, the estrogen-regulated gene encoding a member of the ZIP family of zinc transporters (SLC39A6), has been implicated in both growth and metastasis of estrogen-receptor (ER) positive (+) and negative (-) breast cancer cells. In ER+ breast cancer cells, LIV-1 expression is induced by both estrogen and insulin. In embryonic cells, LIV-1 has also been negatively associated with the expression of the cell adhesion protein, E-cadherin (CDH1), thought to play a role in metastasis. In the present study, we investigated the regulation of LIV-1 and its relationship to CDH1 in MDA-MB-231 ER- breast cancer cells. Cells were treated with insulin and EGF for 24 hours and the mRNA concentrations of LIV-1 and CDH1 were analyzed by RT-PCR. EGF treatment induced LIV-1 mRNA by about 2-fold whereas insulin had minor effects. The mRNA expression of CDH1 paralleled that of LIV-1 with these treatments. MDA-MB-231 cells were also transfected with an shRNA construct designed to knock down LIV-1 expression. This procedure reduced LIV-1 mRNA concentrations by approximately 40% and expression of CDH1 was reduced to a similar extent. This positive association between LIV-1 and CDH1 expression in MDA-MB-231 cells suggests that LIV-1 may be a regulator of CDH1 in ER- cells.
To further understand the linkage between LIV-1 and CDH1, expression of SNAI1, thought to be a transcriptional repressor of CDH1, was measured. However, neither EGF nor LIV-1 knockdown altered the expression of SNAI1 suggesting that this factor does not mediate influences of LIV-1 on CDH1 in these cells. We next investigated the expression of another Snail member, SNAI2, to explain the observed effects. EGF tended to decrease SNAI2 expression and LIV-1 knockdown increased its expression. Thus SNAI2 may be a modulator of a more aggressive and hormonally independent type of breast cancer cells. We also used 65Zn to characterize the role of LIV-1 in zinc uptake. Knockdown of LIV-1 reduced 65Zn uptake in parallel to the reduction in LIV-1 expression, demonstrating the important role of this transporter for zinc homeostasis in MDA-MB-231 cells. Overall, our current findings suggest that LIV-1 is regulated by the EGFR signaling pathway in ER- breast cancer cells. SNAI2 is inversely regulated by LIV-1 to repress CDH1, increasing the potential for metastasis.
","abstract_html":"<p>LIV-1, the estrogen-regulated gene encoding a member of the<sup> </sup>ZIP family of zinc transporters (SLC39A6), has been implicated in both growth and metastasis of<sup> </sup>estrogen-receptor (ER) positive (+) and negative (-) breast cancer cells<em>.<strong> </strong></em>In ER<sup>+</sup> breast cancer cells, LIV-1 expression is induced by both estrogen and insulin. In embryonic cells, LIV-1 has also been negatively associated with the expression of the cell adhesion protein, E-cadherin (CDH1), thought to play a role in metastasis. In the present study, we investigated the regulation of LIV-1 and its relationship to CDH1 in MDA-MB-231 ER<sup>-</sup> breast cancer cells. Cells were treated with insulin and EGF for 24 hours and the mRNA concentrations of LIV-1 and CDH1 were analyzed by RT-PCR. EGF treatment induced LIV-1 mRNA by about 2-fold whereas insulin had minor effects. The mRNA expression of CDH1 paralleled that of LIV-1 with these treatments. MDA-MB-231 cells were also transfected with an shRNA construct designed to knock down LIV-1 expression. This procedure reduced LIV-1 mRNA concentrations by approximately 40% and expression of CDH1 was reduced to a similar extent. This positive association between LIV-1 and CDH1 expression in MDA-MB-231 cells suggests that LIV-1 may be a regulator of CDH1 in ER<sup>-</sup> cells.</p> <p>To further understand the linkage between LIV-1 and CDH1, expression of SNAI1, thought to be a transcriptional repressor of CDH1, was measured. However, neither EGF nor LIV-1 knockdown altered the expression of SNAI1 suggesting that this factor does not mediate influences of LIV-1 on CDH1 in these cells. We next investigated the expression of another Snail member, SNAI2, to explain the observed effects. EGF tended to decrease SNAI2 expression and LIV-1 knockdown increased its expression. Thus SNAI2 may be a modulator of a more aggressive and hormonally independent type of breast cancer cells. We also used <sup>65</sup>Zn to characterize the role of LIV-1 in zinc uptake. Knockdown of LIV-1 reduced<sup> 65</sup>Zn uptake in parallel to the reduction in LIV-1 expression, demonstrating the important role of this transporter for zinc homeostasis in MDA-MB-231 cells. Overall, our current findings suggest that LIV-1 is regulated by the EGFR signaling pathway in ER<sup>- </sup>breast cancer cells. SNAI2 is inversely regulated by LIV-1 to repress CDH1, increasing the potential for metastasis.</p>","abstract_has_math":false,"creators":["Chong, Leelyn"],"institution":null,"degree_name":"Master of Science","degree_level":null,"degree_discipline":"Nutritional Science","degree_department":null,"school":null,"contributors":["Richard Bruno; Ji-Young Lee","Hedley C. Freake"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-06-08T07:00:00Z","date_published":"2011-06-08T07:00:00Z","updated_at":"2026-07-24T06:31:45Z","subjects":["zinc","LIV-1","CDH1","breast cancer"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.lib.uconn.edu/gs_theses/118","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Richard Bruno; Ji-Young Lee","Hedley C. Freake"]},{"key":"dc:creator","label":"Author","values":["Chong, Leelyn"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2011-07-07T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Nutritional Science"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["zinc","LIV-1","CDH1","breast cancer"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.lib.uconn.edu/gs_theses/118"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["LIV-1, the estrogen-regulated gene encoding a member of the ZIP family of zinc transporters (SLC39A6), has been implicated in both growth and metastasis of estrogen-receptor (ER) positive (+) and negative (-) breast cancer cells. In ER+ breast cancer cells, LIV-1 expression is induced by both estrogen and insulin. In embryonic cells, LIV-1 has also been negatively associated with the expression of the cell adhesion protein, E-cadherin (CDH1), thought to play a role in metastasis. In the present study, we investigated the regulation of LIV-1 and its relationship to CDH1 in MDA-MB-231 ER- breast cancer cells. Cells were treated with insulin and EGF for 24 hours and the mRNA concentrations of LIV-1 and CDH1 were analyzed by RT-PCR. EGF treatment induced LIV-1 mRNA by about 2-fold whereas insulin had minor effects. The mRNA expression of CDH1 paralleled that of LIV-1 with these treatments. MDA-MB-231 cells were also transfected with an shRNA construct designed to knock down LIV-1 expression. This procedure reduced LIV-1 mRNA concentrations by approximately 40% and expression of CDH1 was reduced to a similar extent. This positive association between LIV-1 and CDH1 expression in MDA-MB-231 cells suggests that LIV-1 may be a regulator of CDH1 in ER- cells.
To further understand the linkage between LIV-1 and CDH1, expression of SNAI1, thought to be a transcriptional repressor of CDH1, was measured. However, neither EGF nor LIV-1 knockdown altered the expression of SNAI1 suggesting that this factor does not mediate influences of LIV-1 on CDH1 in these cells. We next investigated the expression of another Snail member, SNAI2, to explain the observed effects. EGF tended to decrease SNAI2 expression and LIV-1 knockdown increased its expression. Thus SNAI2 may be a modulator of a more aggressive and hormonally independent type of breast cancer cells. We also used 65Zn to characterize the role of LIV-1 in zinc uptake. Knockdown of LIV-1 reduced 65Zn uptake in parallel to the reduction in LIV-1 expression, demonstrating the important role of this transporter for zinc homeostasis in MDA-MB-231 cells. Overall, our current findings suggest that LIV-1 is regulated by the EGFR signaling pathway in ER- breast cancer cells. SNAI2 is inversely regulated by LIV-1 to repress CDH1, increasing the potential for metastasis.
"]},{"key":"dc:title","label":"Title","values":["The regulation of LIV-1 mRNA in MDA-MB-231 human breast cancer cells and its association with E-cadherin (CDH1)"]}]}],"canonical_facts":{"dc:contributor":["Richard Bruno; Ji-Young Lee","Hedley C. Freake"],"dc:creator":["Chong, Leelyn"],"dc:date.available":["2011-07-07T07:00:00Z"],"dc:description.abstract":["LIV-1, the estrogen-regulated gene encoding a member of the ZIP family of zinc transporters (SLC39A6), has been implicated in both growth and metastasis of estrogen-receptor (ER) positive (+) and negative (-) breast cancer cells. In ER+ breast cancer cells, LIV-1 expression is induced by both estrogen and insulin. In embryonic cells, LIV-1 has also been negatively associated with the expression of the cell adhesion protein, E-cadherin (CDH1), thought to play a role in metastasis. In the present study, we investigated the regulation of LIV-1 and its relationship to CDH1 in MDA-MB-231 ER- breast cancer cells. Cells were treated with insulin and EGF for 24 hours and the mRNA concentrations of LIV-1 and CDH1 were analyzed by RT-PCR. EGF treatment induced LIV-1 mRNA by about 2-fold whereas insulin had minor effects. The mRNA expression of CDH1 paralleled that of LIV-1 with these treatments. MDA-MB-231 cells were also transfected with an shRNA construct designed to knock down LIV-1 expression. This procedure reduced LIV-1 mRNA concentrations by approximately 40% and expression of CDH1 was reduced to a similar extent. This positive association between LIV-1 and CDH1 expression in MDA-MB-231 cells suggests that LIV-1 may be a regulator of CDH1 in ER- cells.
To further understand the linkage between LIV-1 and CDH1, expression of SNAI1, thought to be a transcriptional repressor of CDH1, was measured. However, neither EGF nor LIV-1 knockdown altered the expression of SNAI1 suggesting that this factor does not mediate influences of LIV-1 on CDH1 in these cells. We next investigated the expression of another Snail member, SNAI2, to explain the observed effects. EGF tended to decrease SNAI2 expression and LIV-1 knockdown increased its expression. Thus SNAI2 may be a modulator of a more aggressive and hormonally independent type of breast cancer cells. We also used 65Zn to characterize the role of LIV-1 in zinc uptake. Knockdown of LIV-1 reduced 65Zn uptake in parallel to the reduction in LIV-1 expression, demonstrating the important role of this transporter for zinc homeostasis in MDA-MB-231 cells. Overall, our current findings suggest that LIV-1 is regulated by the EGFR signaling pathway in ER- breast cancer cells. SNAI2 is inversely regulated by LIV-1 to repress CDH1, increasing the potential for metastasis.
"],"dc:identifier":["https://digitalcommons.lib.uconn.edu/gs_theses/118"],"dc:subject":["zinc","LIV-1","CDH1","breast cancer"],"dc:title":["The regulation of LIV-1 mRNA in MDA-MB-231 human breast cancer cells and its association with E-cadherin (CDH1)"],"thesis:degree_discipline":["Nutritional Science"],"thesis:degree_name":["Master of Science"]},"updated_at":"2026-07-24T06:31:45Z"}