Identification of a highly specific surface marker of T‐cell acute lymphoblastic leukemia and neuroblastoma as a new member of the transmembrane 4 superfamily

Takagi, Shin; Fujikawa, Kiyomi; Imai, Toshio; Fukuhara, Norio; Fukudome, Kenji; Minegishi, Masayoshi; Tsuchiya, Shigeru; Konno, Tasuke; Hinuma, Yorio; Yoshie, Osamu

doi:10.1002/ijc.2910610519

Cited by 60 publications

(50 citation statements)

References 22 publications

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“…Beside clone C4.8, another novel member of the TM-4 family which is also di erentially expressed in HPK IA cells was identi®ed (clone C19.6). This cDNA also shares its highest homologies with the TALLA-1 tumor associated antigen (Takagi et al, 1995) but is distinct from clone C4.8. Unfortunately, no expression of this gene could be detected in cervical biopsies by RNA ± RNA-in situ hybridization.…”

Section: Discussionmentioning

confidence: 94%

Identification of novel molecular markers which correlate with HPV-induced tumor progression

et al. 1998

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High risk HPVs (human papillomaviruses) are causally involved in the development of cervical cancer. However, other factors, such as somatic genetic alterations also play a decisive role in malignant conversion of cervical keratinocytes. Mutations and chromosomal aberrations are known to in¯uence the pattern of gene expression. Therefore we used the recently developed RT ± PCR based method of di erential display of mRNAs to detect di erences in gene expression which correlate with tumorigenicity. Non-tumorigenic HPV16-immortalized human foreskin keratinocytes (HPK IA) were compared with their tumorigenic counterparts and 49 di erent genes were identi®ed which were either up-or downregulated. The identi®ed genes encode proteins of the cytoskeleton and the extracellular matrix, the nuclear splicing apparatus, transcription regulators and membrane-associated proteins. The expression pattern of all genes was also examined by RNA ± RNA in situ hybridization in biopsies of normal cervical epithelium, precancerous lesions and cancers. Two genes, C4.8 and C21.7, are of particular interest because their expression is upregulated in a subset of high grade precancerous lesions and in over 58% of cancers. These two genes may therefore be considered as putative progression markers. C4.8 is a new member of the transmembrane 4 (TM-4) protein family which includes tumor-associated antigens such as CD63 and TAPA-1, whereas C21.7 shows no signi®cant homologies to any known genes or proteins.

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Section: Discussionmentioning

confidence: 94%

Identification of novel molecular markers which correlate with HPV-induced tumor progression

et al. 1998

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“…In contrast to CD9, CD63 and CD82, 2 further members of the TM4SF family are more strongly expressed in the course of tumorigenesis. A15 (Talla-1) was identified as a highly specific surface marker of T-cell acute lymphoblastic leukemia and neuroblastoma, 20,21 whereas CO-029 is frequently highly expressed in stomach, colon and pancreas carcinoma. 22 Our study provides evidence that NET-1/C4.8 represents another member of the tetraspanin family of proteins, whose upregulation is clearly associated with carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Identification of a new proliferation‐associated protein NET‐1/C4.8 characteristic for a subset of high‐grade cervical intraepithelial neoplasia and cervical carcinomas

Wollscheid

Kühne-Heid

Stein

et al. 2002

Intl Journal of Cancer

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A large number of genes are known to be differentially expressed at distinct steps of carcinogenesis. By using a cell culture model system for cervical cancer, we had previously identified several genes that were more strongly expressed when comparing normal cervical epithelium with cervical intraepithelial neoplasia (CIN) and cervical cancer. In our study, we show that one of these genes, C4.8, is identical to NET-1, which is a new member of the tetraspanin family of proteins. By generating a mouse polyclonal antiserum against the major extracellular domain of the protein, we could detect NET-1/C4.8 expression both after ectopic expression of the gene in cell cultures and in cryostat sections of cervical biopsies. Moreover, immunohistochemic analyses of normal cervical epithelium, metaplasia, condyloma and CIN of different severity suggest that NET-1/C4.8 expression is associated with neoplastic cell proliferation. Notably, expression of the protein throughout the entire epithelium is only evident for a subset of CIN3. The potential importance for this gene in cervical carcinogenesis is underlined by an invariably strong expression in all undifferentiated squamous cell cancers examined. This indicates that this gene may be of prognostic value.

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“…Anti-TM4SF mAbs used were as follows: anti-CD9, DU-ALL-1 (Sigma); anti-CD53, HD77 (40); anti-CD81, M38 (41); anti-CD82, M104 (41); anti-CD151, 5C11 (42); and anti-A15/TALLA1, B2D (43). mAbs to PKC␣, PKC␥, and phosphatidylinositol 3-kinase (PI 3-K) were obtained from Transduction Laboratories (Lexington, KY).…”

Section: Methodsmentioning

confidence: 99%

Transmembrane-4 Superfamily Proteins Associate with Activated Protein Kinase C (PKC) and Link PKC to Specific β1 Integrins

Zhang

Bontrager

Hemler

2001

Journal of Biological Chemistry

323

290

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Translocation of conventional protein kinases C (PKCs) to the plasma membrane leads to their specific association with transmembrane-4 superfamily (TM4SF; tetraspanin) proteins (CD9, CD53, CD81, CD82, and CD151), as demonstrated by reciprocal co-immunoprecipitation and covalent cross-linking experiments. Although formation and maintenance of TM4SF-PKC complexes are not dependent on integrins, TM4SF proteins can act as linker molecules, recruiting PKC into proximity with specific integrins. Previous studies showed that the extracellular large loop of TM4SF proteins determines integrin associations. In contrast, specificity for PKC association probably resides within cytoplasmic tails or the first two transmembrane domains of TM4SF proteins, as seen from studies with chimeric CD9 molecules. Consistent with a TM4SF linker function, only those integrins (␣ 3 ␤ 1 , ␣ 6 ␤ 1 , and a chimeric "X3TC5" ␣ 3 mutant) that associated strongly with tetraspanins were found in association with PKC. We propose that PKC-TM4SF-integrin structures represent a novel type of signaling complex. The simultaneous binding of TM4SF proteins to the extracellular domains of the integrin ␣ 3 subunit and to intracellular PKC helps to explain why the integrin ␣3 extracellular domain is needed for both intracellular PKC recruitment and PKC-dependent phosphorylation of the ␣ 3 integrin cytoplasmic tail.

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Identification of a highly specific surface marker of T‐cell acute lymphoblastic leukemia and neuroblastoma as a new member of the transmembrane 4 superfamily

Cited by 60 publications

References 22 publications

Identification of novel molecular markers which correlate with HPV-induced tumor progression

Identification of novel molecular markers which correlate with HPV-induced tumor progression

Identification of a new proliferation‐associated protein NET‐1/C4.8 characteristic for a subset of high‐grade cervical intraepithelial neoplasia and cervical carcinomas

Transmembrane-4 Superfamily Proteins Associate with Activated Protein Kinase C (PKC) and Link PKC to Specific β1 Integrins

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