title: Female-specific rectal carcinogenesis in cyclin D1b transgenic mice.
abstract: Human cyclin D1 generates two major isoforms via alternative splicing: cyclin D1a and cyclin D1b. Cyclin D1b is hardly expressed in normal tissues but is frequently expressed in certain types of cancer tissues. To clarify the oncogenic potential of cyclin D1b variant, we developed cyclin D1b transgenic (Tg) mice and analyzed their phenotypes. We detected rectal tumors in 63% (15/24) of the female Tg mice. All rectal tumors had the histological characteristics similar to human sessile serrated adenoma/polyps (SSA/Ps). Adenocarcinomas were also found in 53% (8/15) of the rectal tumors, suggesting that these adenocarcinomas originated from the SSA/P-like lesions. No rectal tumors were found in the ovariectomized female cyclin D1b Tg mice (0/10), indicating that ovarian hormones played a critical role in rectal carcinogenesis in these Tg mice. Both phosphorylation of Erk, without activating MEK, and expression of estrogen receptor β were elevated in the rectal tumors of female cyclin D1b Tg mice compared with normal rectums of female wild-type mice. In addition, we established a cell line, D1bTgRT, derived from a rectal cancer of female Tg mouse. Small interfering RNA-induced cyclin D1b knockdown in this cell line suppressed Erk phosphorylation, anchorage-independent growth, cell invasiveness and tumorigenicity in nude mice. In humans, expression of cyclin D1b messenger RNA was detected in 17% (1/6) of colorectal cancer cell lines and 9.7% (3/31) of colorectal cancer tissues. Taken together, these results indicate that cyclin D1b expression contributes to the female- specific rectal carcinogenesis in mouse model.
authors: Department of Urology, Kohka Public Hospital, Minakuchi-cho, Kohka, Shiga 528-0014, Japan.
authors: Chul Jang
authors: CJ
authors: Kim
authors: Yukihiro
authors: Y
authors: Tambe
authors: Ken-Ichi
authors: K
authors: Mukaisho
authors: Hiroyuki
authors: H
authors: Sugihara
authors: Takahiro
authors: T
authors: Isono
authors: Hiromichi
authors: H
authors: Sonoda
authors: Tomoharu
authors: T
authors: Shimizu
authors: Gen
authors: G
authors: Kondoh
authors: Hirokazu
authors: H
authors: Inoue
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D010052:Ovariectomy; D012004:Rectal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery
chemical_list: C530104:CCND1 protein, human; D047629:Estrogen Receptor beta; D012739:Gonadal Steroid Hormones; D019938:Cyclin D1