| Note | |
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| Entity | Prostate cancer |
| Note | Androgen up-regulates LRP16 expression in both mRNA and protein levels in androgen-sensitive prostate cancer cells such as LNCaP cells, but not in prostate cancer cells without overexpression of LRP16, which significantly stimulates cell growth in the presence of androgen. Reversely, inhibition of the endogenous LRP16 in androgen-sensitive prostate cancer cells markedly diminishes androgen-stimulated cell growth. LRP16 is not only a target of AR in androgen-sensitive prostate cancer cells, but also a coactivator of AR. By the AR-LRP16 feedback pathway, LRP16 may play an important role in the progression of androgen-sensitive prostate cancers. |
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| Entity | Estrogen-dependent breast cancer and endometrial cancer |
| Note | LRP16 is not only a target gene of ERalpha, but also an ERalpha coactivator. LRP16 overexpression significantly promotes MCF-7 cell proliferation. Reversely, knockdown of LRP16 in MCF-7 cells markedly impaired estrogen-stimulated ERalpha activity and cell growth. LRP16 overexpression was observed in more than 30% primary breast cancers.
LRP16 represses E-cadherin (a molecule associated with cell adhesion and tumor metastasis) expression through antagonizing the binding of ERalpha to the E-cadherin promoter. Inhibition of LRP16 expression in both estrogen-responsive MCF-7 breast cancer and Ishikawa endometrial cancer cells significantly attenuates their invasive capacity.
Collectively, LRP16 may be involved in the progression of estrogen-dependent cancers. |
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| Entity | Gastric carcinoma |
| Note | The expression level of LRP16 in primary gastric carcinoma tissues was significantly higher than that in normal mucosa tissues. In addition, overexpression of LRP16 was positively linked with tumor size, depth of invasion, lymph node metastasis, distant metastasis and TNM stage. Higher expression of LRP16 predicts a poor prognosis of gastric carcinoma patients. |
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| Entity | Colorectal carcinoma |
| Note | The higher expression level of LRP16 was found to be positively associated with the poor differentiation of primary human colorectal carcinomas. In addition, higher expression of LRP16 in primary human colorectal carcinomas was also linked to poor prognosis of patients. |
| Prognosis | LRP16 overexpression predicts a poor prognosis in several tumors. |
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| Entity | in myelodysplastic syndrome |
| Hybrid/Mutated Gene | A kind of chromosome rearrangement t(11;21)(q13;q22), involved in RUNX1 (also known as AML1) and LRP16, was found in a patient with monocytic leukemia evolving from myelodysplastic syndrome (MDS). The fusion junction of hybrid gene RUNX1-LRP16 has two types, involving either exon 5 or exon 6 of RUNX1 and exon 2 of LRP16. The reciprocal LRP16-RUNX1 chimera is a fusion between exon 1 of LRP16 and exon 7 of RUNX1. |
| Abnormal Protein | Both RUNX1 (exon 5)-LRP16 and RUNX1 (exon 6)-LRP16 retain the RUNT domain (RD) of RUNX1 and the macro domain of LRP16, whereas reciprocal LRP16-RUNX1 retains the transactivation domain (TA) of RUNX1. The formation of fusion protein RUNX1-LRP16 may lead to the inhibition of myeloid differentiation and contributes to leukemia genesis. |
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| Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler. |
| Gottschalk AJ, Timinszky G, Kong SE, Jin J, Cai Y, Swanson SK, Washburn MP, Florens L, Ladurner AG, Conaway JW, Conaway RC. |
| Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13770-4. Epub 2009 Aug 6. |
| PMID 19666485 |
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| Up-regulation of LRP16 mRNA by 17beta-estradiol through activation of estrogen receptor alpha (ERalpha), but not ERbeta, and promotion of human breast cancer MCF-7 cell proliferation: a preliminary report. |
| Han WD, Mu YM, Lu XC, Xu ZM, Li XJ, Yu L, Song HJ, Li M, Lu JM, Zhao YL, Pan CY. |
| Endocr Relat Cancer. 2003 Jun;10(2):217-24. |
| PMID 12790785 |
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| GC-rich promoter elements maximally confers estrogen-induced transactivation of LRP16 gene through ERalpha/Sp1 interaction in MCF-7 cells. |
| Han WD, Si YL, Zhao YL, Li Q, Wu ZQ, Hao HJ, Song HJ. |
| J Steroid Biochem Mol Biol. 2008 Mar;109(1-2):47-56. Epub 2007 Dec 8. |
| PMID 18206366 |
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| Estrogenically regulated LRP16 interacts with estrogen receptor alpha and enhances the receptor's transcriptional activity. |
| Han WD, Zhao YL, Meng YG, Zang L, Wu ZQ, Li Q, Si YL, Huang K, Ba JM, Morinaga H, Nomura M, Mu YM. |
| Endocr Relat Cancer. 2007 Sep;14(3):741-53. |
| PMID 17914104 |
| |
| LRP16 is fused to RUNX1 in monocytic leukemia cell line with t(11;21)(q13;q22). |
| Imagama S, Abe A, Suzuki M, Hayakawa F, Katsumi A, Emi N, Kiyoi H, Naoe T. |
| Eur J Haematol. 2007 Jul;79(1):25-31. Epub 2007 May 28. |
| PMID 17532767 |
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| Clinicopathological significance of LRP16 protein in 336 gastric carcinoma patients. |
| Li YZ, Zhao P, Han WD. |
| World J Gastroenterol. 2009 Oct 14;15(38):4833-7. |
| PMID 19824120 |
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| [Expression and clinical significance of LRP16 gene in human breast cancer] |
| Liao DX, Han WD, Zhao YL, Pu YD, Mu YM, Luo CH, Li XH. |
| Ai Zheng. 2006 Jul;25(7):866-70. |
| PMID 16831279 |
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| Keratin 18 attenuates estrogen receptor alpha-mediated signaling by sequestering LRP16 in cytoplasm. |
| Meng Y, Wu Z, Yin X, Zhao Y, Chen M, Si Y, Yang J, Fu X, Han W. |
| BMC Cell Biol. 2009 Dec 26;10:96. |
| PMID 20035625 |
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| Induction of the LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the downregulation of E-cadherin. |
| Meng YG, Han WD, Zhao YL, Huang K, Si YL, Wu ZQ, Mu YM. |
| Cell Res. 2007 Oct;17(10):869-80. |
| PMID 17893710 |
| |
| Differential activities of cellular and viral macro domain proteins in binding of ADP-ribose metabolites. |
| Neuvonen M, Ahola T. |
| J Mol Biol. 2009 Jan 9;385(1):212-25. Epub 2008 Nov 1. |
| PMID 18983849 |
| |
| Differential induction of LRP16 by liganded and unliganded estrogen receptor alpha in SKOV3 ovarian carcinoma cells. |
| Tian L, Wu Z, Zhao Y, Meng Y, Si Y, Fu X, Mu Y, Han W. |
| J Endocrinol. 2009 Jul;202(1):167-77. Epub 2009 Apr 29. |
| PMID 19403568 |
| |
| A macrodomain-containing histone rearranges chromatin upon sensing PARP1 activation. |
| Timinszky G, Till S, Hassa PO, Hothorn M, Kustatscher G, Nijmeijer B, Colombelli J, Altmeyer M, Stelzer EH, Scheffzek K, Hottiger MO, Ladurner AG. |
| Nat Struct Mol Biol. 2009 Sep;16(9):923-9. Epub 2009 Aug 13. |
| PMID 19680243 |
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| Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma. |
| Xi HQ, Zhao P, Han WD. |
| World J Gastroenterol. 2010 Apr 7;16(13):1644-8. |
| PMID 20355243 |
| |
| The single-macro domain protein LRP16 is an essential cofactor of androgen receptor. |
| Yang J, Zhao YL, Wu ZQ, Si YL, Meng YG, Fu XB, Mu YM, Han WD. |
| Endocr Relat Cancer. 2009 Mar;16(1):139-53. Epub 2008 Nov 20. |
| PMID 19022849 |
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| Mechanism of transcriptional regulation of LRP16 gene expression by 17-beta estradiol in MCF-7 human breast cancer cells. |
| Zhao YL, Han WD, Li Q, Mu YM, Lu XC, Yu L, Song HJ, Li X, Lu JM, Pan CY. |
| J Mol Endocrinol. 2005 Feb;34(1):77-89. |
| PMID 15691879 |
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