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Regulation of LIV‐1 expression in breast cancer cells
Author(s) -
Grattan Bruce J,
Sankavaram Kavitha,
Freake Hedley C
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.897.25
Subject(s) - fulvestrant , estrogen receptor , endocrinology , estrogen , medicine , cell culture , cancer cell , insulin , biology , chemistry , cancer , breast cancer , genetics
LIV‐1 was originally described in MCF7 breast cancer cells as an estrogen regulated transcript and then subsequently identified as a zinc transporter (SLC39A6/ZIP‐6). Given the requirements of zinc for growth, we hypothesized that LIV‐1 might be increased by factors stimulating cell division, both in MCF7 estrogen receptor positive and in receptor negative MDA‐MB‐231 cells. Cells were treated with 17 β‐estradiol, insulin, IGF‐1 and EGF and LIV‐1 mRNA concentrations assessed by RT‐PCR. Contrary to previous studies, neither estradiol nor insulin at physiological concentrations induced LIV‐1 expression in MCF7 cells, though expression was reduced by the anti‐estrogen fulvestrant. In MDA‐MB‐231 cells, insulin exposure enhanced LIV‐1 mRNA levels whereas treatment with EGF induced LIV‐1 at low concentrations and inhibited the expression of this gene at higher concentrations. As a ZIP family transporter, it was hypothesized that sequestering of extracellular zinc using the zinc specific chelator diethylenetriaminepentaacetate (DTPA) would enhance the expression of LIV‐1. However, it was found that while treatment with DTPA increased LIV‐1 mRNA concentrations in MCF7 cells, it reduced expression in MDA‐MB‐231 cells. Thus, LIV‐1 is differentially regulated in these two breast cancer cell lines, both by hormones and by zinc availability.