In situ expression patterns of melanoma-inhibiting activity (MIA) in melanomas and breast cancers

Bosserhoff, Anja‐Katrin; Moser, Markus; Hein, Rüdiger; Landthaler, Míchael; Buettner, Reinhard

doi:10.1002/(sici)1096-9896(199903)187:4<446::aid-path267>3.0.co;2-y

Cited by 68 publications

(46 citation statements)

References 15 publications

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“…21 Immunohistochemical staining of ErbB-2 was performed using HercepTest (DAKO, Glostrup, Denmark) as described before. 22 Evaluation of immunohistochemical staining Evaluation of HercepTest was performed observing the staining pattern of cell membranes as set in the criteria specified by Dako for interpretation.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Distinct spatial expression patterns of AP-2alpha and AP-2gamma in non-neoplastic human breast and breast cancer

et al. 2005

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Although transcription factors AP-2alpha and AP-2gamma have been implicated in the control of estrogen receptor (ER) and ErbB-2, their impact for breast cancer is still controversial. To better understand the role of AP-2 proteins in mammary neoplasia, the analysis of their spatial expression pattern in normal breast and breast cancer is required. A total of 51 specimens of female breast cancer patients and a tissue microarray containing 93 additional female breast cancer cases were immunohistochemically stained for AP-2alpha, AP2gamma, ER and ErbB-2. In 70 cases of the tissue microarray, survival data comprising a period of up to 30 years were present. In non-neoplastic breast tissue, AP-2alpha was expressed in the inner glandular cell layer while AP-2gamma was expressed in the outer myoepithelial cell layer. Ductal carcinoma in situ revealed strongly AP-2alpha-positive tumor cells surrounded by a layer of AP-2gamma-positive myoepithelial cells. In invasive carcinoma, expression of AP-2alpha and AP-2gamma was variable. High expression of ER and AP2alpha showed better survival rates than low expression of these markers. AP-2gamma expression had no effect on survival. These results for the first time reveal a distinct spatial expression pattern of AP-2alpha and AP-2gamma in normal breast and in ductal carcinoma in situ with specific AP-2gamma expression in myoepithelium. High ER and AP-2alpha expression in invasive breast cancer showed favorable survival rates. Therefore, AP-2alpha expression seems to be associated with better prognosis of breast cancer. AP-2gamma expression has no influence on survival reflecting that myoepithelial cells are not involved in the neoplastic process.

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Section: Immunohistochemistrymentioning

confidence: 99%

Distinct spatial expression patterns of AP-2alpha and AP-2gamma in non-neoplastic human breast and breast cancer

et al. 2005

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“…Later, it was shown that MIA is expressed in malignant melanomas and chondrosarcomas (Bosserhoff et al, 1996(Bosserhoff et al, , 1999. Today, increased serum levels of MIA serve as a reliable clinical marker to detect and monitor metastatic disease in patients with malignant melanomas (Bosserhoff et al, 1997;Stahlecker et al, 2000), indicating an important role for them in tumor progression and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Functional role of MIA in melanocytes and early development of melanoma

et al. 2004

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The protein MIA (melanoma inhibitory activity) is highly expressed in malignant melanomas but not in melanocytes. Furthermore, expression of MIA correlates with tumor progression in vivo. Here, MIA-dependent changes of gene expression after long-term inhibition of MIA expression in the human melanoma cell line HMB2 were investigated. Primarily, we observed characteristic changes in cell morphology, and also found re-established cell-cell contacts in MIA-deficient cell clones grown in monolayer culture. Real-time reverse transcription-polymerase chain reaction (RT-PCR) showed a downregulation of N-cadherin expression and a reinduction of E-cadherin expression in the MIA-deficient cell clones. Further, both cancer cDNA array and protein arrays verified a marked downregulation of several other melanoma-associated genes (e.g. membrane-type 1 matrix metalloproteinase tissue-type plasminogen activator integrin b3, secreted protein acidic and rich in cysteins and fibronectin) in the MIA-deficient melanoma cells, confirmed by real-time RT-PCR and Western blotting. As all these molecules are associated with migration, the effect of MIA on migration of human primary melanocytes was analysed. In the presence of MIA, we observed enhanced migratory ability of melanocytic cells, induction of melanoma-associated genes as well as inhibition of apoptosis due to anoikis. These results suggest that expression of MIA promotes melanoma progression by inducing further melanoma-associated genes.

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“…Virtually all primary and metastatic melanoma cells, but not normal melanocytes, express and secrete MIA to a high extent, such that MIA serum levels serve as a marker for malignant melanoma (Bosserhoff et al, 1997b, a;Deichmann et al, 1999). Neoplastic expression of MIA has also been observed in mammacarcinoma (Bosserhoff et al, 1999b), ovarian cancer (Bosserhoff et al, 1999a), and various gastrointestinal carcinomas (Wagner et al, 2000). Although MIA is thought to play an important role in cartilage formation, the cellular actions of MIA are not clear.…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of an Inner Ear-Expressed Human Melanoma Inhibitory Activity (MIA)-like Gene (MIAL) with a Frequent Polymorphism That Abolishes Translation

et al. 2001

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To discover new cochlea-specific genes as candidate genes for nonsyndromic hearing impairment, we searched in The Institute of Genome Research database for expressed sequence tags isolated from the cochlea only. This led to the cloning and characterization of a human gene named melanoma inhibitory activity-like (MIAL; HGMW-approved symbol OTOR alias MIAL) gene. In situ hybridization revealed MIAL expression in a cell layer beneath the sensory epithelium of cochlea and vestibule of human fetal inner ear. No other human tissue, except fetal brain, showed expression of MIAL when analyzed by in situ hybridization or reverse transcription-polymerase chain reaction. The cDNA of the mouse homologue was also cloned and mapped about 80 cM from the top of mouse chromosome 2. In mouse, Mial was also expressed in the cochlea and the vestibule of the inner ear, as well as in brain, eye, limb, and ovary. Expression in mammalian cell cultures showed that MIAL is translated as an ϳ15-kDa polypeptide that is assembled into a covalently linked homodimer, modified by sulfation, and secreted from the cells via the Golgi apparatus. In the human MIAL gene, a frequent polymorphism was discovered in the translation initiation codon (ACG instead of ATG). Of 505 individuals, 48 (9.5%) were ATG/ ACG heterozygous and 1 (0.2%) was homozygous for ACG. No MIAL protein was synthesized in cells transfected with cDNA of the ACG allele. The inner earrestricted expression pattern and the existence of an inactive allele suggest that MIAL may contribute to inner-ear dysfunction in humans.

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In situ expression patterns of melanoma-inhibiting activity (MIA) in melanomas and breast cancers

Cited by 68 publications

References 15 publications

Distinct spatial expression patterns of AP-2alpha and AP-2gamma in non-neoplastic human breast and breast cancer

Distinct spatial expression patterns of AP-2alpha and AP-2gamma in non-neoplastic human breast and breast cancer

Functional role of MIA in melanocytes and early development of melanoma

Identification and Characterization of an Inner Ear-Expressed Human Melanoma Inhibitory Activity (MIA)-like Gene (MIAL) with a Frequent Polymorphism That Abolishes Translation

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