scholarly journals Reproductive Disturbances, Pituitary Lactotrope Adenomas, and Mammary Gland Tumors in Transgenic Female Mice Producing High Levels of Human Chorionic Gonadotropin

Endocrinology ◽  
2002 ◽  
Vol 143 (10) ◽  
pp. 4084-4095 ◽  
Author(s):  
Susana B. Rulli ◽  
Aino Kuorelahti ◽  
Öznur Karaer ◽  
Lauri J. Pelliniemi ◽  
Matti Poutanen ◽  
...  
Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3694-3703 ◽  
Author(s):  
Aino Kuorelahti ◽  
Susana Rulli ◽  
Ilpo Huhtaniemi ◽  
Matti Poutanen

Transgenic (TG) mice expressing human chorionic gonadotropin (hCG) β-subunit under the ubiquitin C promoter, presenting with a moderately elevated level of LH/hCG bioactivity develop multiple neoplasms secondary to the endocrine abnormalities, including mammary gland tumors after the age of 9 months. The increased levels of circulating estradiol, progesterone, and prolactin of the TG females after puberty boost the lobuloalveolar development in the mammary gland resulting ultimately in the formation of estrogen and progesterone receptor-negative, malignant tumors. These tumors have a similar histopathology with those observed in TG mice with activated wnt/β-catenin pathway, showing increased expression of β-catenin, also a common finding in human breast tumors. Transdifferentiation is observed in mammary tumors of the hCGβ TG mice, accompanied by abnormal expression of the Wnt genes in the tumorous and nontumorous mammary gland tissue. Specifically we found increased expression of Wnt5b in the TG mammary glands at the age of 3 months and up-regulation of Wnt7b and -5b in the subsequently appearing tumors. Importantly, hCG was found to up-regulate these wnt ligands in mouse mammary gland, independent of the changes in ovarian steroidogenesis. Thus, the hCGβ-overexpressing TG mice represent a novel model that links enhanced hCG action to dysregulated wnt signaling in the mammary gland, resulting in β-catenin-stabilizing mammary tumorigenesis. The novel finding of hCG up-regulating wnt7b and wnt5b could contribute to pregnancy-induced breast cancer in humans.


2014 ◽  
Vol 390 (1-2) ◽  
pp. 102-111 ◽  
Author(s):  
Betina Gonzalez ◽  
Laura D. Ratner ◽  
María J. Scerbo ◽  
Noelia P. Di Giorgio ◽  
Matti Poutanen ◽  
...  

Endocrinology ◽  
2004 ◽  
Vol 145 (10) ◽  
pp. 4763-4774 ◽  
Author(s):  
Choon Kiat Ong ◽  
Chuan Young Ng ◽  
Caine Leong ◽  
Chee Pang Ng ◽  
Chye Sun Ong ◽  
...  

Abstract We previously identified a novel pregnancy-induced growth inhibitory gene, OKL38. To develop a rat model for further characterization of OKL38’s role in the initiation and progression of breast and ovarian cancer, we now report the cloning and characterization of three novel rat OKL38 cDNAs that are derived through alternative splicing and differential promoter usage. These three transcripts differ in their 5′ untranslated regions but share a common open reading frame that encoded for a 52-kDa protein. OKL38 is mapped to chromosome 19, spanning a region of approximately 15 kb, and contains eight exons. Differential expression of these three rat OKL38 transcripts was observed in liver, kidney, ovary, mammary gland, and uterus. In situ hybridization localized the rat OKL38 transcripts to the luminal epithelial cells of the rat mammary gland and to the granulosa cells in the rat ovary. In vivo studies showed that the RtOKL38-2.0 transcript and protein were regulated by human chorionic gonadotropin in the rat mammary gland and ovary. Importantly, overexpression of RtOKL38-enhanced green florescence protein fusion protein in Buffalo rat liver cells resulted in growth inhibition and cell death. Our present findings suggest that OKL38 may function as an effector for human chorionic gonadotropin protection against mammary carcinogenesis, and the availability of the three rat OKL38 cDNAs may help to elucidate the possible role of OKL38 in cellular growth, differentiation, and carcinogenesis.


1998 ◽  
Vol 37 (08) ◽  
pp. 297-298 ◽  
Author(s):  
A. Özet ◽  
A. Arpaci ◽  
S. Kömiircü ◽  
G. Üçkaya

Summary50 years old man suffering from primary lung adenocarcinoma presented with high levels of both beta subunit human chorionic gonadotropin (βHCG) and cancer antigen 15-3 (CA 15-3) in the absence of elevated carcinoembrionic antigen (CEA), alfa fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9). Although βHCG or CA 15-3 high levels were reported in adenocarcinoma of lung, this is the first report of a patient with high levels of both markers.


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