Differential Expression of Metallothionein 1 and 2 Isoforms in Breast Cancer Lines with Different Invasive Potential

Tai, Siew-Kian; Tan, Owen; Chow, Vincent T.K.; Jin, Rong; Jones, J. Louise; Tan, Puay‐Hoon; Jayasurya, Anita; Bay, Boon‐Huat

doi:10.1016/s0002-9440(10)63559-6

Cited by 63 publications

(57 citation statements)

References 55 publications

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“…27 However, we did not find such a correlation. In contrast, MDA-MB-231 cells, the most invasive line in our study, exhibited the lowest level of PCho among the cancer cell-lines whereas T47D cells, which exhibit low tumorigenicity and are non metastatic when implanted in immunodeficiency mice, 70,71 showed the highest PCho level. In addition, the concentrations of PCho reported by Aboagye and Bhujwalla differed from those obtained by us based on NTP concentration of approximately 4 mM.…”

Section: Discussioncontrasting

confidence: 65%

Phosphocholine as a biomarker of breast cancer: Molecular and biochemical studies

Eliyahu¹,

Kreizman²,

Degani³

2007

Intl Journal of Cancer

206

223

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The discovery of metabolic and molecular markers that help improving the detection and diagnosis of breast cancer is an important goal to be achieved. A high composite-choline signal in magnetic resonance spectra of breast lesions has been demonstrated to improve the accuracy of breast cancer diagnosis. In the present study we revealed the principal molecular and biochemical steps associated with the induction of choline metabolism and phosphocholine accumulation in human breast cancer cell-lines in comparison with normal human mammary epithelial cells. We found upregulation of the expression levels of specific choline transporters: organic cation transporter-2 and choline high affinity transporter-1, as well as of the enzyme choline kinase a in the cancerous cells in comparison with that in the normal mammary epithelial cells. The expression levels of choline transporter like-1, organic cation transporter-1 and choline kinase b were similar in normal and cancerous cells. We further showed that choline transport rates and choline kinase activity indeed increased by several fold in the cancer cells leading to the elevation of phosphocholine. The results strongly suggest that phosphocholine can serve as a biomarker of breast cancer reflecting upregulation of specific choline transporters and choline kinase genes. ' 2007 Wiley-Liss, Inc.

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Section: Discussioncontrasting

confidence: 65%

Phosphocholine as a biomarker of breast cancer: Molecular and biochemical studies

Eliyahu¹,

Kreizman²,

Degani³

2007

Intl Journal of Cancer

206

223

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“…Although metatypic BCC is regarded as an aggressive subtype of BCC, it manifested the lowest MT-I/II expression of the analyzed subtypes. We used IHC techniques to determine MT-I/II expression, but recent studies have shown that only particular MT-I/II isoforms may contribute to cancer cell aggressiveness in some tumor types [31][32][33][34][35]. In our study, we noted the highest Ki-67 antigen expression in this subtype.…”

Section: Discussionmentioning

confidence: 55%

Expression of metallothionein I/II and Ki-67 antigen in various histological types of basal cell carcinoma

Bieniek¹,

Puła²,

Piotrowska³

et al. 2012

Folia Histochem Cytobiol.

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Basal cell carcinoma (BCC) is the most frequent skin cancer, with many different histological subtypes. Recent studies have investigated the expression of proliferative markers, but little is known about the expression of metallothioneins (MT) in different histological subtypes of this cancer and their impact on proliferation intensity in BCC. In this study, we examined MT-I/II expression by immunohistochemistry in 58 different histological subtypes of BCC (38 nodular, six adenoid, eight infiltrative, and six metatypic cases) and correlated its expression with tumor size and Ki-67 proliferation rate. Statistical analysis revealed no significant differences in the expression of studied markers in regard to the histological subtype. A positive correlation between MT and Ki-67 expression was observed for all the studied cases (r = 0.26; p = 0.049), but was even stronger in the metatypic subtype of BCC (r = 0.85; p = 0.033). MT and Ki-67 expression did not correlate with tumor size. In conclusion, it seems that metallothioneins may have an impact on the proliferation rate of BCC, but further studies are required to determine whether MT may be a risk factor of recurrences.

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“…An inverse relationship between the expression of MTs and PLU-1/JARID1B is also seen in breast cancer cell lines. Thus, high levels of the MTs MT1E and MT2A are found in the breast cancer cell lines Hs578T and MDA-MB-231, which express low levels of PLU-1, while lessinvasive estrogen receptor (ER)-positive cell lines, such as MCF7, ZR75, and T47D, show low expression levels of the MT proteins but high levels of PLU-1/JARID1B (3,4,46,74).…”

Section: Discussionmentioning

confidence: 99%

Functional Analysis of the Transcription Repressor PLU-1/JARID1B

Scibetta

Santangelo

Coleman

et al. 2007

Molecular and Cellular Biology

120

119

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The PLU-1/JARID1B nuclear protein, which is upregulated in breast cancers, belongs to the ARID family of DNA binding proteins and has strong transcriptional repression activity. To identify the target genes regulated by PLU-1/JARID1B, we overexpressed or silenced the human PLU-1/JARID1B gene in human mammary epithelial cells by using adenovirus and RNA interference systems, respectively, and then applied microarray analysis to identify candidate genes. A total of 100 genes showed inversely correlated differential expression in the two systems. Most of the candidate genes were downregulated by the overexpression of PLU-1/JARID1B, including the MT genes, the tumor suppressor gene BRCA1, and genes involved in the regulation of the M phase of the mitotic cell cycle. Chromatin immunoprecipitation assays confirmed that the metallothionein 1H (MT1H), -1F, and -1X genes are direct transcriptional targets of PLU-1/JARID1B in vivo. Furthermore, the level of trimethyl H3K4 of the MT1H promoter was increased following silencing of PLU-1/JARID1B. Both the PLU-1/JARID1B protein and the ARID domain selectively bound CG-rich DNA. The GCACA/C motif, which is abundant in metallothionein promoters, was identified as a consensus binding sequence of the PLU-1/ JARID1B ARID domain. As expected from the microarray data, cells overexpressing PLU-1/JARID1B have an impaired G 2 /M checkpoint. Our study provides insight into the molecular function of the breast cancerassociated transcriptional repressor PLU-1/JARID1B.The PLU-1 nuclear protein is expressed in most primary breast cancers and breast cancer cell lines (4, 46), while its expression in normal adult tissues is largely restricted to testes (46), where it is expressed in spermatogonia and in specific stages of meiosis (48). However, significant expression is also seen in the murine pregnant mammary gland (4) and in the embryonic mammary bud (4, 47). Thus, in addition to being elevated in breast cancer, PLU-1 is involved in the development and differentiation of the mammary gland.The PLU-1 gene encodes a 1,544-amino-acid multidomain protein that is exclusively localized to the nucleus. Sequence homology analysis shows that it contains several conserved domains, including the ARID DNA binding domain (AT-richinteracting domain), plant homeodomain/leukemia-associated protein domains (PHD domains), Jumonji domains, and putative nuclear localization signals (46). The ARID domain, the N-terminal and C-terminal Jumonji domains (JmJN and JmJC), two of the plant homeodomain domains, and a novel Trp/Tyr/Phe/Cys domain (the PLU domain), which overlaps the JmJC domain (62), are conserved in the four members of the JARID1 subfamily of the larger family of ARID proteins (15 proteins to date) (86). Although their sequence homology is high, these proteins appear to have diverse functions, with JARID1A (RBP2) being involved in activating transcription from nuclear receptors (14), PLU-1 (now referred to as PLU-1/JARID1B) being a strong transcriptional repressor (75, 88), and JARID1C (the SMCX gene) ...

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Differential Expression of Metallothionein 1 and 2 Isoforms in Breast Cancer Lines with Different Invasive Potential

Cited by 63 publications

References 55 publications

Phosphocholine as a biomarker of breast cancer: Molecular and biochemical studies

Phosphocholine as a biomarker of breast cancer: Molecular and biochemical studies

Expression of metallothionein I/II and Ki-67 antigen in various histological types of basal cell carcinoma

Functional Analysis of the Transcription Repressor PLU-1/JARID1B

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