Expression of HOXC8 is inversely related to the progression and metastasis of pancreatic ductal adenocarcinoma

Abstract

Background:The transcription factor HOXC8 regulates many genes involved in tumour progression. This study was to investigate the role of HOXC8 in pancreatic ductal adenocarcinoma (PDAC) growth and metastasis.Methods:The Hoxc8 expression was determined in 15 PDAC cell lines and human specimens by RT–polymerase chain reaction and/or immunohistochemistry. The effects of HOXC8 silencing by RNA interference were investigated by functional tests.Results:The Hoxc8 mRNA expression in PDAC cell lines was negatively related to their growth in vivo. Except for Suit2-007 cells, only those with low Hoxc8 mRNA expression grew in nude rats. Successful down-regulation of HOXC8 expression caused increased proliferation, migration (P⩽0.05) and colony formation (P⩽0.05) in Suit2-007, Panc-1 and MIA PaCa-2 PDAC cells, respectively. The Hoxc8 mRNA levels in diseased human pancreas tissues were significantly increased over normal in PDAC and autoimmune chronic pancreatitis specimens (P<0.01, respectively), but negatively related to tumour stage (P=0.09). In primary and metastatic tumour samples, immunohistochemical staining for HOXC8 was stronger in surrounding than in neoplastic tissues. Furthermore, grading of primary carcinomas was negatively associated with HOXC8 staining (P=0.03). Liver metastases showed the lowest HOXC8 expression of all neoplastic lesions.Conclusion:These data indicate that HOXC8 expression is inversely related to PDAC progression and metastasis.

Upregulation of MGP by HOXC8 promotes the proliferation, migration, and EMT processes of triple‐negative breast cancer

“…Among these genes, human HOXC8 gene is located at chromosome 12q13.13, and plays a role in a number of physiological processes, including embryonic development, cell proliferation, and differentiation, and so forth . Recent studies showed that HOXC8 is also involved in tumorigenesis, including breast, prostate, lung, cervical, and pancreatic cancers, by facilitating cell proliferation and metastasis …”

HOXC8 (homeobox C8)

“…The gene is also expressed in both the neural tube and the somites in the prospective thorax (Pollock et al, 1992;Shashikant and Ruddle, 1996). Cancers: Elevated HOXC8 expression is detected in breast cancer (Li et al, 2014;Li et al, 2010), cervical cancer (Alami et al, 1999), prostate cancer (Waltregny et al, 2002), esophageal cancer (Du et al, 2014), pancreatic cancer (Adwan et al, 2011). Organs: HOXC8 is expressed in hematopoietic organs, brain, breast, placenta, liver, bone marrow, kidney, intestine and nervous systems, etc.…”

“…Down-regulation of HOXC8 expression causes increased proliferation, migration and colony formation, which indicates that HOXC8 is a negative regulator of pancreatic cancer cell growth and metastasis. In primary and metastatic tumor samples, immunohistochemistry staining shows that grading of primary carcinomas is negatively associated with the extent and intensity of HOXC8 staining (Adwan et al, 2011).…”

“…Stem cells: HOXC8 is expressed in vascular wallresident multi-potent stem cells (VW-MPSCs), and silencing its expression significantly reduces cell sprouting capacity and increases expression of the smooth muscle cells marker genes (Klein et al, 2013). Cancers: HOXC8 plays an essential role in cancer development, including breast, prostate, cervical and pancreatic cancers by facilitating cell migration and invasion (Adwan et al, 2011;Alami et al, 1999;Axlund et al, 2010;Du et al, 2014;Li et al, 2010).…”

Análise funcional e expressão do gene homeobox HOXB7 em adenocarcinomas pancreáticos ductais

“…Este relato enriqueceu o trabalho desenvolvido porYamashita et al (2006), no qual foi demonstrado o aumento de expressão dos genes homeobox HOXB7, HOXA13 e HOXB13 tanto no câncer de ovário quanto nas linhagens celulares deste derivadas em comparação aos controles normais. O aumento da expressão do gene HOXB13 foi também evidenciado porMiao et al (2007), os quais expuseram a participação do homeobox não só na promoção do crescimento tumoral in vivo, mas também na resistência à apoptose mediada por tamoxifeno.Hayashida et al (2010), por sua vez, relataram o aumento de expressão de HOXB9 em câncer de mama, estando a elevada expressão associada ao potencial invasivo, visto que, in vivo, este fator de transcrição promove a formação de tumores de mama volumosos e bem vascularizados, os quais metastatizam para o pulmão.Enquanto muitos estudos demonstraram o aumento de expressão dos genes HOX em câncer, outros relataram a redução, como exposto porAdwan et al (2011), cujo trabalho evidenciou a diminuição da expressão do RNA mensageiro do gene HOXC8 em adenocarcinomas pancreáticos ductais quando comparados ao tecidos normais e amostras de pancreatite crônica. A técnica de imuno-histoquímica, por sua vez, revelou uma marcação mais forte no tecido circundante do que nos tecidos neoplásicos.Os padrões de expressão dos genes HOXB5, HOXB6, HOXB2 e HOXD13 também foram caracterizados em câncer de pancreático.…”