Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cathepsins B and L, implicated in the progression of malignant tumors, are regulated by a family of endogenous inhibitors referred to as the cystatins. Cystatin M was identified by differential display as down-regulated gene in metastatic breast cancer cells. However, this finding has yet to be confirmed in clinical breast cancer specimens. Our objective is to examine the expression levels of cystatins C, M, and cathepsins B and L mRNA in breast cancer cells isolated by laser capture microdissection. The mRNA and protein levels of cathepsin B, L, and cystatin C and M in breast cancer specimens were determined utilizing laser capture microdissection/RT-PCR, Western blotting, and immunohistochemical methods. Expression levels of either cystatin M or C were not significantly different between lymph node-positive and -negative breast carcinomas. Increased expression levels of both cystatin M and C correlated significantly with larger tumor size. Cystatin M mRNA was detected by in situ hybridization in both primary and metastatic breast cancer cells. Our findings are at variance with a previous report proposing a metastasis suppressive function for cystatin M. Therefore, additional studies in a larger series with adequate follow-up are necessary to elucidate the biologic significance of cystatin M expression in breast cancer metastasis.
 ...
PMID:Expression analysis of cystatin C and M in laser-capture microdissectioned human breast cancer cells--a preliminary study. 1579 17

CST6 is a breast tumor suppressor gene that is expressed in normal breast epithelium, but is epigenetically silenced as a consequence of promoter hypermethylation in metastatic breast cancer cell lines. In the current study, we investigated the expression and methylation status of CST6 in primary breast tumors and lymph node metastases. 25/45 (56%) primary tumors and 17/20 (85%) lymph node metastases expressed significantly lower levels of cystatin M compared to normal breast tissue. Bisulfite sequencing demonstrated CST6 promoter hypermethylation in 11/23 (48%) neoplastic lesions analyzed, including 3/11 (27%) primary tumors and 8/12 (67%) lymph node metastases. In most cases (12/23, 52%), the expression of cystatin M directly reflected CST6 promoter methylation status. In remaining lesions (8/23, 35%) loss of cystatin M was not associated with CST6 promoter hypermethylation, indicating that other mechanisms can account for loss of CST6 expression. These results show that methylation-dependent silencing of CST6 occurs in a subset of primary breast cancers, but more frequently in metastatic lesions, possibly reflecting progression-related genomic events. To examine this possibility, primary breast tumors and matched lymph node metastases were analyzed. In 2/3 (67%) patients, primary tumors were positive for cystatin M and negative for CST6 promoter methylation, and matched metastatic lesions lacked cystatin M expression and CST6 was hypermethylated. This observation suggests that progression-related epigenetic alterations in CST6 gene expression can accompany metastatic spread from a primary tumor site. Overall, the results of the current investigation suggest that methylation-dependent epigenetic silencing of CST6 represents an important mechanism for loss of CST6 during breast tumorigenesis and/or progression to metastasis.
 ...
PMID:Methylation-dependent silencing of CST6 in primary human breast tumors and metastatic lesions. 1754 Mar 67