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CASC5  -  cancer susceptibility candidate 5

Homo sapiens

Synonyms: AF15Q14, AF15q14, ALL1-fused gene from chromosome 15q14 protein, Blinkin, Bub-linking kinetochore protein, ...
 
 
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Disease relevance of CASC5

  • AF15q14 appears identical to an mRNA previously found to be expressed in melanoma rendered nontumorigenic by microcell-mediated introduction of normal chromosome 6, suggesting the gene may function normally to suppress cell growth and/or enhance maturation [1].
  • We examined the relationship between D40 expression and clinico-pathological characteristics of tumours in primary lung cancer [2].
  • D40/AF15q14 is the first gene in the cancer/testis family for which expression is related to the smoking habits of cancer patients [2].
 

High impact information on CASC5

  • Four other human proteins of unknown function (c20orf172, DC8, PMF1 and KIAA1570) correspond to yeast Mis12-Mtw1 complex components and are shown to be required for chromosome segregation in HeLa cells using RNA interference (RNAi) [3].
  • A small region of VCAM including D40, QIDS, can be replaced by the similar ICAM-1 sequence, GIET, without affecting function or epitopes, indicating that this region is part of a general integrin-binding structure rather than a determinant of binding specificity for a particular integrin [4].
  • Recent studies have shown that MLL is fused to AF15q14 in the t(11;15) [5].
  • MPFYVE is also located on chromosome 15, approximately 170 kb telomeric to AF15q14 [5].
  • The gene on chromosome 15, AF15q14, was cloned recently in a patient with AML-M4 [1].
 

Biological context of CASC5

  • Sequencing of AF15q14 cDNA revealed a putative open reading frame of 1833 amino acids that had no homology with any other known protein [6].
  • However, both the MLL and AF15q14 breakpoints in these patients differed: in the previously reported AML-M4, both gene breaks were within exons, while in our ALL case the MLL break is intronic and the AF15q14 break is exonic [1].
  • In an attempt to clone a novel human gene, we screened a cDNA library derived from a human B cell line and obtained a cDNA clone that we refer to as D40 [2].
  • A search for public databases for sequence homologies showed that the D40 gene is identical to AF15q14 [2].
  • This is consistent with the finding that the amino-acid sequence at the amino terminal of the D40 protein lacks a hydrophobic signal peptide that is required for proteins to translocate to the membrane [7].
 

Anatomical context of CASC5

  • The normal AF15q14 transcripts of approximately 8.5 kb in size, are expressed in different tumoral cell lines, in a variety of normal tissues, and in all the foetal tissues tested [6].
  • D40 mRNA is predominantly expressed in normal testis tissue [2].
  • In the acrosome, D40 protein expression is observed not inside but outside the acrosome membrane [7].
  • Immunohistochemical studies have revealed that D40 protein is highly expressed in spermatocytes and in the pre-acrosome of round spermatids [7].
  • Expression of D40 protein is observed in the acrosome of ejaculated spermatozoa as well, although the level is low compared with that in the pre-acrosome of spermatids [7].
 

Associations of CASC5 with chemical compounds

  • Flow cytometric and immunocytochemical analyses showed expression of cellular adhesion molecules ICAM-I and LFA-3, and MHC-Class-I (MCF7/D40 only), to be decreased in the doxorubicin-selected MDR-sublines, whereas expression of CD56 (Leu 19) was strongly up-regulated in 8226/Dox40 [8].
  • Gonadally intact males began one of three AAS treatments at puberty (D40): testosterone propionate (T), stanozolol (S), T+S, or vehicle control [9].
  • D40 is a cell surface protein belonging to the tumor necrosis factor (TNF) receptor family [10].
  • Furifosmin exhibited greater washout from both MCF7/S and MCF7/D40 than sestamibi, while tetrofosmin washout was greater than sestamibi in MCF7/D40 only [11].
  • TSH, thyroid hormone levels (TG, T4, T3, rT3, FT4 and FT3) and TBG were measured by radioimmunoassays at D0, D10, D20, D30 and D40 [12].
 

Analytical, diagnostic and therapeutic context of CASC5

  • Fluorescent in situ hybridization (FISH) was performed to determine the chromosomal region that D40 gene resides [13].
  • Anaesthetized mice with MCF7/S (MIBI, n=9; GLA, n=8) and MCF7/D40 (MIBI, n=6; GLA, n=5) tumours were imaged using a high-resolution SPECT system called FASTSPECT [14].
  • Expression of MDR P-glycoprotein (Pgp) in the tumours was demonstrated in the MCF7/D40 tumours by western blotting, not in the MCF7/S tumours [14].

References

  1. Characterization of the MLL partner gene AF15q14 involved in t(11;15)(q23;q14). Kuefer, M.U., Chinwalla, V., Zeleznik-Le, N.J., Behm, F.G., Naeve, C.W., Rakestraw, K.M., Mukatira, S.T., Raimondi, S.C., Morris, S.W. Oncogene (2003) [Pubmed]
  2. Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers. Takimoto, M., Wei, G., Dosaka-Akita, H., Mao, P., Kondo, S., Sakuragi, N., Chiba, I., Miura, T., Itoh, N., Sasao, T., Koya, R.C., Tsukamoto, T., Fujimoto, S., Katoh, H., Kuzumaki, N. Br. J. Cancer (2002) [Pubmed]
  3. A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Obuse, C., Iwasaki, O., Kiyomitsu, T., Goshima, G., Toyoda, Y., Yanagida, M. Nat. Cell Biol. (2004) [Pubmed]
  4. Arrangement of domains, and amino acid residues required for binding of vascular cell adhesion molecule-1 to its counter-receptor VLA-4 (alpha 4 beta 1). Osborn, L., Vassallo, C., Browning, B.G., Tizard, R., Haskard, D.O., Benjamin, C.D., Dougas, I., Kirchhausen, T. J. Cell Biol. (1994) [Pubmed]
  5. A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15. Chinwalla, V., Chien, A., Odero, M., Neilly, M.B., Zeleznik-Le, N.J., Rowley, J.D. Oncogene (2003) [Pubmed]
  6. AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14). Hayette, S., Tigaud, I., Vanier, A., Martel, S., Corbo, L., Charrin, C., Beillard, E., Deleage, G., Magaud, J.P., Rimokh, R. Oncogene (2000) [Pubmed]
  7. The protein encoded by cancer/testis gene D40/AF15q14 is localized in spermatocytes, acrosomes of spermatids and ejaculated spermatozoa. Sasao, T., Itoh, N., Takano, H., Watanabe, S., Wei, G., Tsukamoto, T., Kuzumaki, N., Takimoto, M. Reproduction (2004) [Pubmed]
  8. Altered expression of P-glycoprotein and cellular adhesion molecules on human multi-drug-resistant tumor cells does not affect their susceptibility to NK- and LAK-mediated cytotoxicity. Scheper, R.J., Dalton, W.S., Grogan, T.M., Schlosser, A., Bellamy, W.T., Taylor, C.W., Scuderi, P., Spier, C. Int. J. Cancer (1991) [Pubmed]
  9. Factors influencing aggression toward females by male rats exposed to anabolic androgenic steroids during puberty. Cunningham, R.L., McGinnis, M.Y. Hormones and behavior (2007) [Pubmed]
  10. Monocyte CD40 expression in severe sepsis. Sugimoto, K., Galle, C., Preiser, J.C., Creteur, J., Vincent, J.L., Pradier, O. Shock (2003) [Pubmed]
  11. Imaging recognition of multidrug resistance in human breast tumors using 99mTc-labeled monocationic agents and a high-resolution stationary SPECT system. Liu, Z., Stevenson, G.D., Barrett, H.H., Kastis, G.A., Bettan, M., Furenlid, L.R., Wilson, D.W., Woolfenden, J.M. Nucl. Med. Biol. (2004) [Pubmed]
  12. The thyroid-system function in preterm infants of postmenstrual ages of 31 weeks or less: evidence for a "transient lazy thyroid system". Eggermont, E., Vanderschueren-Lodeweyckx, M., De Nayer, P., Smeets, E., Vanacker, G., Cornette, C., Jaeken, J., Devlieger, H., Eeckels, R., Beckers, C. Helvetica paediatrica acta. (1984) [Pubmed]
  13. Chromosomal assignment of a novel human gene D40. Wei, G., Takimoto, M., Yoshida, I., Mao, P.Z., Koya, R.C., Miura, T., Kuzumaki, N. Nucleic Acids Symp. Ser. (1999) [Pubmed]
  14. 99mTc glucarate high-resolution imaging of drug sensitive and drug resistant human breast cancer xenografts in SCID mice. Liu, Z., Stevenson, G.D., Barrett, H.H., Kastis, G.A., Bettan, M., Furenlid, L.R., Wilson, D.W., Woolfenden, J.M., Pak, K.Y. Nuclear medicine communications. (2004) [Pubmed]
 
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